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Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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A variety of organ-specific autoimmune diseases can be induced in
rodent strains that are not normally susceptible by
interfering with normal T cell maturation or by causing a partial T
cell deficiency (5). In general, a defined subset of T
cells from syngeneic healthy donors can prevent the development of
autoimmunity on transfer to lymphopenic recipients, indicating that the
normal immune system contains immunoregulatory T cells that can prevent
the activation of autoreactive T cells (6). For example,
Powrie et al. (7) have shown that colitis can be induced
in immunodeficient SCID mice by transfer of the
CD45RBhigh subset of CD4+ T
cells from normal mice, but not by the
CD45RBlow population. The
CD45RBlow population, when transferred together
with the CD45RBhigh population, completely
inhibited development of the disease. Evidence for the existence of
regulatory T cells has also been obtained in both the bio-breeding rat
and nonobese diabetic (NOD) mouse strains that spontaneously
develop autoimmune diabetes (8, 9).
CD4+ T cells that express TCRs encoded by
endogenous 
/ß-chain genes are also likely to be responsible for
the relative disease resistance of mice that express a transgenic
(Tg)2 TCR specific for
a peptide from myelin basic protein (10).
Studies using two different model systems have demonstrated that a
potent CD4+ immunoregulatory T cell population
can be defined by expression of the IL-2R -chain (CD25). In the
first model system (11, 12), genetically susceptible mice
that were thymectomized on day 3 of life (d3Tx) developed
organ-specific autoimmune disease involving one or more organs. The
disease process was mediated by CD4+ T cells;
however, CD4+ T cells from normal adult mice
could inhibit the development of disease in the d3Tx animals if they
were transferred by day 14 of life. Furthermore, the inhibitory
activity was completely contained within the minor (10%) subset of
CD4+ T cells that coexpressed CD25 (13, 14). In the second model, when
CD4+CD25+ T cells were
depleted from CD4+ T cells isolated from
peripheral lymphoid tissues of normal adult mice and the remaining
CD4+CD25- cells injected
into nu/nu mice recipients, the recipients developed a high
incidence of organ-specific autoimmune disease (13, 15).
Again, cotransfer of populations enriched in
CD4+CD25+ prevented the
induction of disease by the
CD4+CD25- population. In
addition, we have also demonstrated that
CD4+CD25+ T cells can
inhibit the capacity of a cloned line of autoantigen-specific effector
cells to transfer disease to nu/nu recipients
(16). Thus, the
CD4+CD25+ population can
inhibit both the induction and effector function of autoreactive T
cells.
We have previously developed an in vitro model system for suppressor T cell function and have demonstrated that the CD4+CD25+ T cell population present in normal mice was a potent inhibitor of polyclonal T cell activation (17). Suppression was mediated by a cytokine-independent, cell contact-dependent mechanism that required activation of the CD4+CD25+ cells via the TCR. The CD4+CD25+ cells inhibited the induction of IL-2 production in the responder CD4+CD25- population. Although the responses to soluble anti-CD3 in the presence of normal T-depleted spleen cells were easily suppressed, the responses to plate-bound anti-CD3 were unaffected and suppression could be overcome by the addition of exogenous IL-2 or by enhancing endogenous IL-2 production by the addition of anti-CD28 to the cultures.
In this report, we extend our in vitro studies of the function of the CD4+CD25+ population and demonstrate that they appear to be a homogeneous population of suppressors that do not contain memory or activated T cells. Although our previous studies suggested that the target of the suppressor population was actually the APC rather than the responding T cell, we now demonstrate that CD4+CD25+ cells act through an APC-independent mechanism. In addition, we show that CD4+CD25+ T cells present in the peripheral lymphoid tissues of TCR Tg mice can inhibit Ag-specific proliferation of TCR Tg cells specific for the same Ag. However, once the CD4+CD25+ TCR Tg T cells are activated by their cognate Ag, their suppressor effector function is completely Ag nonspecific. Furthermore, we have generated short-term cell lines by stimulation of CD4+CD25+ cells with anti-CD3 and IL-2. Such cell lines remained anergic when stimulated with anti-CD3, but exhibited enhanced Ag nonspecific suppressor cell function that no longer required engagement of their TCR. Collectively, these studies are most compatible with a model in which CD4+CD25+ cells require activation with specific Ag to develop their suppressive activity; however, once stimulated, they are competent to suppress in an Ag-independent manner.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Female BALB/c and C57BL/6 mice were obtained from the National Cancer Institute (Frederick, MD). Hemagglutinin (HA) TCR Tg (18) and pigeon cytochrome c (PCC) TCR Tg (19) mice were maintained at Taconic (Germantown, NY) under National Institute of Allergy and Infectious Diseases contract. HNT TCR Tg mice were obtained from D. Lo (The Scripps Institute, La Jolla, CA) (20) and were bred in our facilities. P815 cells transfected with B7-2 were obtained from L. Lanier (21)
Media, reagents, and Abs
All cells were grown in RPMI 1640 (Biofluids, Rockville, MD) supplemented with 10% heat-inactivated FCS, 100 U/ml penicillin, 100 µg/ml streptomycin, 2 mM L-glutamine, 10 mM HEPES, 0.1 mM nonessential amino acids, 1 mM sodium pyruvate (all from Biofluids, Rockville, MD), and 50 µM 2-ME (Sigma, St. Louis, MO). Biotin-anti-CD25 (7D4), FITC-streptavidin, PE-anti-CD45RB (16A), PE-anti-CD62L (Mel-14), PE-anti-CD69, FITC-anti-CD69, PE anti-CD38, PE anti-B7-2, FITC-anti-B220, FITC-anti-Kb, PE-anti-Kb FITC-anti-Fas, and purified anti-CD3 (2C11) were purchased from PharMingen (San Diego, CA). PE-anti-CD4 was purchased from Becton Dickinson (Mountain View, CA). Tricolor-anti-CD4 was purchased from Caltag (Burlingame, CA). Human rIL-2 was purchased from Peprotech (Rocky Hill, NJ). Flow cytometry analysis was analyzed using CellQuest software (Becton Dickinson). HA110–119, PCC88–104, and HNT126–138 peptides were synthesized and purified by HPLC by the Laboratory of Molecular Structure, Peptide Synthesis Laboratory (National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD) and used at 32 µM, 0.1 µM, and 1 µg/ml final concentration, respectively.
Cell purification
CD4+CD25+ cells were
purified as previously described (17). The purity of
CD4+CD25+ cells typically
ranged from 88 to 95%. For some experiments,
CD4+CD25+ cells were
purified by flow cytometry on a FACStar Cell Sorter (Becton Dickinson).
T-depleted spleen cells (T
S) were used as APC and were prepared by
first lysing the erythrocytes with ACK lysis buffer, followed by
treatment with anti-Thy 1.2 culture supernatant (HO-13.4) and
rabbit C for 45 min at 370C. The cells were then irradiated at 3000
rad. LPS-TS were made by treating TS with 10 µg/ml LPS for
48 h. Cells were fixed in 0.5% paraformaldehyde for 30 min at
37°C. To generate IL-2-treated
CD4+CD25+ cells,
CD4+CD25+ cells (typically
1–2 x 106), purified by cell sorting, were
cultured with an equivalent number of APC, 0.5 µg/ml anti-CD3,
and 5 ng/ml IL-2 for 3 days and were then split and cultured in medium
containing IL-2 for an additional 3–4 days.
Proliferation assays
CD4+CD25- cells (5 x 104) were cultured in 96-well plates (0.2 ml) with APC (5 x 104), 0.5 µg/ml anti-CD3, and the indicated numbers of CD4+CD25+ cells for 72 h at 37°C/7% CO2. Cultures were pulsed with [3H]TdR for the last 6 h of culture. All experiments were set up in triplicate.
Cell cycle analysis
CD4+CD25- cells purified from C57BL/6 mice were cultured with an equivalent number of APC from BL/6 mice and 0.5 µg/ml anti-CD3 in the absence or presence of CD4+CD25+ cells (2.5 x 104) purified from BALB/c mice. The cells were cultured for 96 h and stained and processed as described (22).
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Because the CD4+CD25+
comprise 10% of the CD4+ T cells in normal mouse
peripheral lymphoid tissues, it remained possible that this population
contained activated T cells that had been induced to express CD25 by
exposure to environmental Ags in vivo. In addition, the
CD4+CD25+ population had an
unusual pattern of expression of membrane markers that are associated
with memory/activated cells. Notably, the
CD4+CD25+ population lacked
the CD45RBhigh subset of T cells and consisted
only of CD45RBint and
CD45RBlow cells. On the other hand, the
CD4+CD25+ population only
contained a modest increase in CD62Llow cells
(35% vs 25%) and CD69+ (35% vs 8%) T cells
when compared with the
CD4+CD25- population (Fig. 1
). Approximately, 60% of the
CD25+ cells expressed CD38, which has recently
been defined by Read et al. (23) as a marker for T cells
with in vitro immunosuppressive activity very similar to the
CD4+CD25+ cells. We
therefore attempted to identify a population within the
CD4+CD25+ pool that might
have enhanced or diminished immunosuppressive functions based on the
differential expression of one of the activation/memory markers.
However, as shown in Fig. 1, any subpopulation of T cells that
expressed CD25 was a potent inhibitor of the proliferative response of
CD4+CD25- T cells to
anti-CD3. Although minor differences were observed between some of
the subpopulations in different experiments, no consistent
subpopulation with an altered suppressor function could be identified.
It should be pointed out that the assay used in this study could
readily detect a population which lacked suppressor activity as we have
previously shown that CD25+ T cells from d3Tx
animals, that lack suppressor function in vivo, that failed to suppress
in vitro, and that induction of CD25 expression on
CD25- cells by TCR stimulation also failed to
result in the induction of suppressor function (17).
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Our previous studies suggested that
CD4+CD25+ cells might
inhibit proliferation of
CD4+CD25- cells by acting
upon the APC either by inhibiting the induction of costimulatory
molecules or by competing for costimulatory signals. We first
investigated the possibility that
CD4+CD25+ cells inhibited
the induction of costimulatory molecules by examining CD86 expression
by flow cytometry. As shown in Fig. 2A, CD86 was not expressed on
APC cultured alone, but was up-regulated on most B220-positive cells
after 48 h of culture with purified CD4+ T
cells and anti-CD3. When
CD4+CD25+ cells were added,
CD86 expression was not affected. In addition, up-regulation of CD40
and ICAM-1 expression was not inhibited in the presence of the
CD25+ cells (data not shown). To further confirm
that CD4+CD25+ cells did
not inhibit proliferation of
CD4+CD25- cells by
inhibiting the induction of expression or functional activation of
other molecules involved in costimulation or cell adhesion on the APC,
CD4+CD25- cells were
stimulated with APC that were already fully competent to provide
costimulation. Following stimulation of T-depleted spleen cells with
LPS for 48 h, nearly 100% of the B220 positive cells expressed
CD86 at high levels (data not shown). When these LPS-activated
T-depleted spleen cells were used as APC,
CD4+CD25+ cells were still
capable of inhibiting proliferation, regardless of whether the APC were
irradiated or fixed (Fig. 2B). Similar results were seen
when P815 cells stably transfected with CD86 were used as APC. These
results also argue against the possibility that the
CD25+ T cells inhibit accessory cell function by
preventing the up-regulation or activation of cell interaction
molecules other than CD86.
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C). Significant proliferative responses were observed at
the lowest concentration of APC (2500/well), and this response was
almost completely inhibited by the CD25+ cells.
Although the proliferative responses were enhanced by addition of
higher numbers of APC, suppression only decreased from 95% to 75%.
Thus, it is very unlikely that
CD4+CD25+ cells compete for
the delivery of costimulatory molecules. CD4+CD25+ cells induce cell cycle arrest
Our previous studies demonstrated that
CD4+CD25+ cells did not
appear to kill the responding
CD4+CD25- cells
(17). Although the
CD4+CD25+ cells inhibited
the induction of IL-2 mRNA synthesis by
CD4+CD25- cells, it was
unclear what stage of the T cell activation process was arrested by the
CD4+CD25+ cells. As
suppression of the response to anti-CD3 could be seen with
histoincompatible combinations of suppressors and responders,
CD4+CD25- cells from
C57BL/6 mice were cocultured with
CD4+CD25+ cells from BALB/c
mice and activation markers were examined by flow cytometry on the
Kb-positive responding cells. Following 24 h
of stimulation with anti-CD3, up-regulation of CD25 and CD69 on the
responder cells was observed in the absence or presence of
CD4+CD25+ cells (Fig. 3A). Although the
expression of CD25, CD69, and Fas continued to increase over the next
48 h of culture in the absence of
CD4+CD25+ cells, no further
up-regulation of these markers was seen on responders cultured in the
presence of CD4+CD25+
cells. Furthermore, in the presence of
CD4+CD25+ cells, the
responders did not blast, as indicated by a lack of increase in forward
scatter, and did not progress into the M or S phases of the cell cycle
(Fig. 3B).
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In our initial studies, the requirement for activation of the
suppressor cell via the TCR was apparent as
CD4+CD25+ cells from normal
BALB/c mice could suppress the anti-CD3, but not the Ag (OVA),
response of CD4+ T cells from DO11.10 TCR Tg
mice. Therefore, we were unable to separate the activation signals for
induction of suppressor cell function from the requirements of
responder T cell activation because anti-CD3 was used to stimulate
both cell populations (17). Although we failed to identify
CD4+CD25+ in TCR Tg SCID
mice (14), Takahashi et al. (24) have shown
that CD4+CD25+ cells are
present in the TCR Tg mice on a conventional background; furthermore,
these cells suppressed the proliferative responses of
CD4+CD25- Tg cells
specific for the same peptide. We confirmed these results with
CD4+CD25+ T cells isolated
from mice expressing a Tg TCR specific for peptide 110–119 of
influenza HA. CD4+CD25+
cells from the HA TCR Tg mice inhibited the proliferation of HA TCR Tg
CD4+CD25- T cells
stimulated with anti-CD3 (Fig. 4A) as well as HA peptide
(Fig. 4B), whereas
CD4+CD25+ cells from
normal BALB/c donors inhibited only the anti-CD3 response.
Inhibition could not be overcome by increasing or decreasing the
peptide concentration (data not shown).
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Although the above results suggested that suppression might be Ag
specific, they were also compatible with the possibility that specific
Ag was required for activation of the
CD4+CD25+ cells, but once
activated, suppressor effector function would be nonspecific. We used
two distinct approaches to investigate this possibility and to
determine whether activation of the suppressor and effector required
that their target Ags be presented on the surface of the same APC. In
the first approach, we took advantage of our ability to separate the
activation signals required for suppressor cell function and those
required for responder cell function by mixing
CD4+CD25+ cells isolated
from mice expressing a Tg TCR specific for one peptide MHC complex
(HA110–119/I-Ed) with
CD4+CD25- T cells from TCR
Tg mice which recognized a distinct peptide MHC complex
PCC88–104/I-Ek. When
CD4+CD25- from HA TCR Tg
mice were stimulated with HA peptide in the presence of a fixed ratio
of CD4+CD25+ cells (1:0.5)
from the HA TCR Tg mice, the HA response was inhibited by >95%. More
importantly, HA-specific responses could be inhibited to the same
extent in the presence of
CD4+CD25+ T from PCC TCR Tg
mice and PCC (Fig. 5A).
Inhibition of the HA-specific response by PCC
CD4+CD25+ cells was
dependent upon the presence of PCC peptide and APC that expressed
I-Ek (data not shown). Conversely, the response
to PCC of cells from PCC TCR Tg mice could be inhibited by both
CD4+CD25+ cells from PCC
TCR Tg mice and by
CD4+CD25+ cells from HA TCR
Tg mice (Fig. 5B). Again, suppression of the PCC specific
response by HA CD4+CD25+
cells was dependent upon the presence of HA peptide and APC which
expressed I-Ed as cpm in the absence of HA
peptide were 164,725. Although
CD4+CD25+ cells from PCC
TCR Tg could suppress Ag-specific proliferation of cells from HA TCR Tg
mice by >95%, CD4+CD25+
cells from HA TCR Tg mice consistently suppressed the PCC response by
65% at the fixed ratio of 1:0.5. However, >95% suppression could
be achieved when the ration was increased to 1:1 (data not shown).
Ag-specific responses were suppressed to the same extent when APC were
obtained from the parental strains or from F1
H-2k/d mice (data not shown). Thus, suppression
does not require that the target Ags be presented on the same
APC.
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A). In contrast,
CD4+CD25- cells that were
cultured in the same manner proliferated vigorously when restimulated
with anti-CD3 alone. More importantly, when the cultured
CD4+CD25+ cells were mixed
with fresh CD4+CD25-
responders, they exhibited markedly enhanced suppressor activity (Fig. 6B). As few as 3 x 103 cultured
CD4+CD25+ cells could
suppressed proliferation by 75%, whereas 12 x
103 freshly isolated
CD4+CD25+ cells were
required to produce the same degree of suppression.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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10%) of CD4+ T cells
that expresses CD25 can be identified in normal lymphoid tissues and
exhibits potent immunoregulatory functions in vivo. Transfer of
CD4+CD25- T cells to
immunodeficient recipients results in the development of organ-specific
autoimmunity. Furthermore, the
CD4+CD25+ population
suppresses the induction of autoimmunity following d3Tx and can also
suppress the induction of autoimmune disease by autoreactive T cell
clones. We and others have previously shown that the
CD4+ CD25+ population is
both anergic and suppressive in vitro. The goal of the present studies
was to further characterize the in vitro suppressive activity of this
unique cell population in an attempt to define their cellular target
and the mechanism by which they mediate their suppressive effect. Our previous studies suggested that the APC was the cellular target for the CD4+CD25+ population. CD4+CD25+ T cells only suppressed APC-dependent responses and suppression of T cell proliferation could be overcome by addition of IL-2 or enhancement of IL-2 production by costimulation with anti-CD28. Collectively, these observations suggested that the suppressor population was inhibiting the generation or delivery of costimulatory signals required for IL-2 production. Potent suppression was also observed at low ratios of responders to suppressors (4:1), which was also consistent with the APC as the primary target. One possibility was that the suppressor population acted on the APC to prevent the up-regulation of expression of cell surface molecules involved in costimulation (CD80/CD86). However, in the coculture studies presented here, the up-regulation of expression of CD80/CD86 proceeded normally in the presence of the CD4+CD25+ cells. It also remained possible that the suppressor population deactivated the APC in some unknown manner to prevent the delivery of the costimulatory signal or to prevent the activation of cell surface molecules that mediate the physical interactions involved in intercellular cooperation (25). However, the CD4+CD25+ population continued to exert potent suppressor activity when activated, fixed APC were used as accessory cells. As it is highly unlikely that paraformaldehyde fixed APC would transduce a membrane mediated signal, APC deactivation does not appear to be the mechanism by which the CD4+CD25+ T cells function. Lastly, we considered a simple competition model in which the suppressor population would bind to the APC and prevent the effector cell from receiving a costimulatory signal or a signal for cell adhesion. However, when an excess of viable activated APC were added to cultures, the magnitude of suppression was only slightly diminished. In contrast to the failure of activated APC to overcome suppression, we have previously shown (17) that the addition of anti-CD28 readily abrogates suppression. At present, we do not have an adequate explanation for this discrepancy, but it is likely that the delivery of a direct costimulatory signal to the responder T cell by a stimulatory mAb is more potent than the delivery of costimulation via an activated APC.
Although expression of the CD25 Ag has greatly facilitated the isolation of the suppressor T cell population, CD25 expression can be induced on all T cells following activation, and it seemed likely that the freshly explanted CD25+ cells might be composed of a mixture of suppressor cells and effector cells activated in vivo. We have previously shown that the CD25+ population is heterogeneous for expression of a number of memory/activation markers. Our attempts to subdivide the CD25+ population into suppressors and effectors by the differential expression of these memory/activation markers (CD45, CD62L, CD69, and CD38) were uniformly unsuccessful. Any cell population that expressed CD25 was a potent suppressor of anti-CD3-induced T cell proliferation in vitro. We have not as yet evaluated these same subpopulations for suppressor function in vivo. Studies by Powrie and colleagues (7) have demonstrated that the population of CD4+CD45RBlow cells is a potent suppressor of autoimmune inflammatory bowel disease in vivo. Recently, Read et al. (23) have split the CD4+CD45RBlow population into two subpopulation based on the differential expression of CD38. The CD4+CD45RBlowCD38+ population appears to be very similar to the CD4+CD25+ population in its capacity to suppress T cell activation in vitro, whereas the CD4+CD45RBlowCD38- population appears to contain memory T cells that can easily be activated upon stimulation in vitro and do not mediate suppression in vitro. Read et al. (23) have not reported the properties of CD25-CD38+ cells and we have thus far been unsuccessful in isolating this population. As both CD25+CD38+ and CD25+CD38- were indistinguishable in our assays, expression of CD25 may therefore be the most specific marker of T cells with immunoregulatory function in vitro.
Our previous studies on the in vitro activity of the
CD4+CD25+ T cells were all
performed with anti-CD3 as a polyclonal stimulus of T cell
activation. Although we have ruled out deactivation of the APC or
competition for APC-derived costimulation as the mechanisms for
suppressor T cell function, in the absence of an assay for Ag-specific
suppression, it has been difficult to exclude competition for Ag/MHC as
the basic mechanism operating in this model. We had previously shown
that the CD4+CD25+
population is reduced by 90–95% in mice which express a single Tg TCR
(14). However, as first shown by Takahashi et al.
(24),
CD4+CD25+ T cells in mice
that express a Tg TCR on a conventional background can be identified
although they are present at less than 50% of the level present in
wild-type mice. The specificity of the
CD4+CD25+ T cells which can
be isolated from TCR Tg mice is most likely determined by the
endogenous TCR -chain and not by the Tg -chain as TCR Tg mice on
a SCID background lack the suppressor
CD4+CD25+ lineage. When
CD4+CD25+ T cells from Tg
mice were stimulated with their target peptide Ag, they suppressed the
response of CD4+CD25- Tg T
cells specific for the same peptide. However,
CD4+CD25+ T cells specific
for one peptide/MHC complex could suppress the response of
CD4+CD25- T cells specific
for a distinct peptide/MHC complex and vice versa. Cross-suppression
did not require the presentation of both complexes on the surface of
the same APC as CD4+CD25+
specific for one peptide/MHC complex would suppress the response of
CD4+CD25- T cells specific
for a second peptide/MHC complex even when the Ags were presented by
two distinct populations of APC.
These studies suggested that once activated via the TCR, suppressor
effector function was completely Ag nonspecific. To address this issue,
we stimulated CD4+CD25+ T
cells with anti-CD3 and IL-2 for 7 days. As reported previously,
CD4+CD25+ T cells can be
expanded quite efficiently by this protocol and the stimulated cells
remained anergic and suppressive (24). In fact, their
capacity to suppress anti-CD3 stimulation of
CD4+CD25- T cells was
enhanced 4- to 6-fold when compared with freshly isolated
CD4+CD25+ cells (Fig. 6).
More importantly, in contrast to freshly isolated
CD4+CD25+ cells, activated
CD4+CD25+ cells were
powerful suppressors of the responses of
CD4+CD25- Tg T cells to a
variety of Ags (Table I). There were no
apparent MHC restrictions on this in vitro suppressor activity. The
potent suppressor activity of the activated
CD4+CD25+ cells (70–80%
suppression at ratios of responder:suppressor of 16–20:1) is actually
problematic in terms of understanding the mechanism of suppression. As
we reported for the freshly isolated
CD4+CD25+ T cells,
suppression was also observed when the IL-2-activated
CD4+CD25+ cells were
separated from the responders by a semipermeable membrane and
suppression could not be reversed by a mixture of mAbs specific for
suppressor cytokines (data not shown). Nevertheless, it is very
difficult to exclude the possibility that suppression is mediated by a
short-acting as yet uncharacterized suppressor molecule. Alternatively,
activation of the CD4+CD25+
population during in vitro culture may result in the induction of a
membrane molecule that can rapidly and efficiently induce inhibition of
IL-2 production and cell cycle arrest by repeated hits on the responder
population.
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Footnotes |
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2 Abbreviations used in this paper: Tg, transgenic; d3Tx, thymectomized on day 3 of life; HA, hemagglutinin; PCC, pigeon cytochrome c.
Received for publication August 20, 1999. Accepted for publication October 21, 1999.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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-chains (CD25): breakdown of a single mechanism of self- tolerance causes various autoimmune diseases. J. Immunol. 155:1151.[Abstract]
chain, resistance to clonal deletion and IL-2 dependency. Int. Immunol. 10:371.This article has been cited by other articles:
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  B. Jurgens, U. Hainz, D. Fuchs, T. Felzmann, and A. Heitger Interferon-{gamma}-triggered indoleamine 2,3-dioxygenase competence in human monocyte-derived dendritic cells induces regulatory activity in allogeneic T cells Blood, October 8, 2009; 114(15): 3235 - 3243. [Abstract] [Full Text] [PDF]
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 S. Sakaguchi, K. Wing, Y. Onishi, P. Prieto-Martin, and T. Yamaguchi Regulatory T cells: how do they suppress immune responses? Int. Immunol., October 1, 2009; 21(10): 1105 - 1111. [Abstract] [Full Text] [PDF]
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 L. C. Chen, J. C. Delgado, P. E. Jensen, and X. Chen Direct Expansion of Human Allospecific FoxP3+CD4+ Regulatory T Cells with Allogeneic B Cells for Therapeutic Application J. Immunol., September 15, 2009; 183(6): 4094 - 4102. [Abstract] [Full Text] [PDF]
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W.-p. Zeng, C. Chang, and J.-j. Lai Immune Suppressive Activity and Lack of T Helper Differentiation Are Differentially Regulated in Natural Regulatory T Cells J. Immunol., September 15, 2009; 183(6): 3583 - 3590. [Abstract] [Full Text] [PDF]
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 L. R. Guerin, J. R. Prins, and S. A. Robertson Regulatory T-cells and immune tolerance in pregnancy: a new target for infertility treatment? Hum. Reprod. Update, September 1, 2009; 15(5): 517 - 535. [Abstract] [Full Text] [PDF]
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A. Eljaafari, Y.-P. Li, and P. Miossec IFN-{gamma}, as Secreted during an Alloresponse, Induces Differentiation of Monocytes into Tolerogenic Dendritic Cells, Resulting in FoxP3+ Regulatory T Cell Promotion J. Immunol., September 1, 2009; 183(5): 2932 - 2945. [Abstract] [Full Text] [PDF]
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 Y.-H. Huang, A. L. Zozulya, C. Weidenfeller, N. Schwab, and H. Wiendl T cell suppression by naturally occurring HLA-G-expressing regulatory CD4+ T cells is IL-10-dependent and reversible J. Leukoc. Biol., August 1, 2009; 86(2): 273 - 281. [Abstract] [Full Text] [PDF]
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A. Joetham, K. Takeda, M. Okamoto, C. Taube, H. Matsuda, A. Dakhama, and E. W. Gelfand Antigen Specificity Is not Required for Modulation of Lung Allergic Responses by Naturally Occurring Regulatory T Cells J. Immunol., August 1, 2009; 183(3): 1821 - 1827. [Abstract] [Full Text] [PDF]
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A. L. Szymczak-Workman, C. J. Workman, and D. A. A. Vignali Cutting Edge: Regulatory T Cells Do Not Require Stimulation through Their TCR to Suppress J. Immunol., May 1, 2009; 182(9): 5188 - 5192. [Abstract] [Full Text] [PDF]
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 P. LISSONI, F. BRIVIO, L. FUMAGALLI, G. MESSINA, S. MEREGALLI, G. PORRO, F. ROVELLI, L. VIGORE, E. TISI, and G. D'AMICO Effects of the Conventional Antitumor Therapies Surgery, Chemotherapy, Radiotherapy and Immunotherapy on Regulatory T Lymphocytes in Cancer Patients Anticancer Res, May 1, 2009; 29(5): 1847 - 1852. [Abstract] [Full Text] [PDF]
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 S. Kuboki, N. Sakai, J. Tschop, M. J. Edwards, A. B. Lentsch, and C. C. Caldwell Distinct contributions of CD4+ T cell subsets in hepatic ischemia/reperfusion injury Am J Physiol Gastrointest Liver Physiol, May 1, 2009; 296(5): G1054 - G1059. [Abstract] [Full Text] [PDF]
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 H Kelchtermans, L Geboes, T Mitera, D Huskens, G Leclercq, and P Matthys Activated CD4+CD25+ regulatory T cells inhibit osteoclastogenesis and collagen-induced arthritis Ann Rheum Dis, May 1, 2009; 68(5): 744 - 750. [Abstract] [Full Text] [PDF]
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T. Bopp, N. Dehzad, S. Reuter, M. Klein, N. Ullrich, M. Stassen, H. Schild, R. Buhl, E. Schmitt, and C. Taube Inhibition of cAMP Degradation Improves Regulatory T Cell-Mediated Suppression J. Immunol., April 1, 2009; 182(7): 4017 - 4024. [Abstract] [Full Text] [PDF]
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M. M. Collazo, D. Wood, K. H. T. Paraiso, E. Lund, R. W. Engelman, C.-T. Le, D. Stauch, K. Kotsch, and W. G. Kerr SHIP limits immunoregulatory capacity in the T-cell compartment Blood, March 26, 2009; 113(13): 2934 - 2944. [Abstract] [Full Text] [PDF]
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D. Q. Tran, D. D. Glass, G. Uzel, D. A. Darnell, C. Spalding, S. M. Holland, and E. M. Shevach Analysis of Adhesion Molecules, Target Cells, and Role of IL-2 in Human FOXP3+ Regulatory T Cell Suppressor Function J. Immunol., March 1, 2009; 182(5): 2929 - 2938. [Abstract] [Full Text] [PDF]
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J. M. Ertelt, J. H. Rowe, T. M. Johanns, J. C. Lai, J. B. McLachlan, and S. S. Way Selective Priming and Expansion of Antigen-Specific Foxp3-CD4+ T Cells during Listeria monocytogenes Infection J. Immunol., March 1, 2009; 182(5): 3032 - 3038. [Abstract] [Full Text] [PDF]
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C. Vogtenhuber, M. J. O'Shaughnessy, D. A. A. Vignali, and B. R. Blazar Outgrowth of CD4low/negCD25+ T Cells with Suppressor Function in CD4+CD25+ T Cell Cultures upon Polyclonal Stimulation Ex Vivo J. Immunol., December 15, 2008; 181(12): 8767 - 8775. [Abstract] [Full Text] [PDF]
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R. Sharma, A. C.-Y. Ju, J. T. Kung, S. M. Fu, and S.-T. Ju Rapid and Selective Expansion of Nonclonotypic T Cells in Regulatory T Cell-Deficient, Foreign Antigen-Specific TCR-Transgenic Scurfy Mice: Antigen-Dependent Expansion and TCR Analysis J. Immunol., November 15, 2008; 181(10): 6934 - 6941. [Abstract] [Full Text] [PDF]
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B. Calderon, A. Suri, X. O. Pan, J. C. Mills, and E. R. Unanue IFN-{gamma}-Dependent Regulatory Circuits in Immune Inflammation Highlighted in Diabetes J. Immunol., November 15, 2008; 181(10): 6964 - 6974. [Abstract] [Full Text] [PDF]
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T. Y. Wuest, J. Willette-Brown, S. K. Durum, and A. A. Hurwitz The influence of IL-2 family cytokines on activation and function of naturally occurring regulatory T cells J. Leukoc. Biol., October 1, 2008; 84(4): 973 - 980. [Abstract] [Full Text] [PDF]
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D. R. Tonkin, J. He, G. Barbour, and K. Haskins Regulatory T Cells Prevent Transfer of Type 1 Diabetes in NOD Mice Only When Their Antigen Is Present In Vivo J. Immunol., October 1, 2008; 181(7): 4516 - 4522. [Abstract] [Full Text] [PDF]
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 Y. Ke, G. Jiang, D. Sun, H. J. Kaplan, and H. Shao Ocular Regulatory T Cells Distinguish Monophasic from Recurrent Autoimmune Uveitis Invest. Ophthalmol. Vis. Sci., September 1, 2008; 49(9): 3999 - 4007. [Abstract] [Full Text] [PDF]
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A. Laronne-Bar-On, D. Zipori, and N. Haran-Ghera Increased Regulatory versus Effector T Cell Development Is Associated with Thymus Atrophy in Mouse Models of Multiple Myeloma J. Immunol., September 1, 2008; 181(5): 3714 - 3724. [Abstract] [Full Text] [PDF]
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S. Hao, J. Yuan, S. Xu, M. A. Munegowda, Y. Deng, J. Gordon, Z. Xing, and J. Xiang Antigen Specificity Acquisition of Adoptive CD4+ Regulatory T Cells via Acquired Peptide-MHC Class I Complexes J. Immunol., August 15, 2008; 181(4): 2428 - 2437. [Abstract] [Full Text] [PDF]
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 S. Sehrawat, S. Suvas, P. P. Sarangi, A. Suryawanshi, and B. T. Rouse In Vitro-Generated Antigen-Specific CD4+ CD25+ Foxp3+ Regulatory T Cells Control the Severity of Herpes Simplex Virus-Induced Ocular Immunoinflammatory Lesions J. Virol., July 15, 2008; 82(14): 6838 - 6851. [Abstract] [Full Text] [PDF]
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L. Gil-Guerrero, J. Dotor, I. L. Huibregtse, N. Casares, A. B. Lopez-Vazquez, F. Rudilla, J. I. Riezu-Boj, J. Lopez-Sagaseta, J. Hermida, S. Van Deventer, et al. In Vitro and In Vivo Down-Regulation of Regulatory T Cell Activity with a Peptide Inhibitor of TGF-{beta}1 J. Immunol., July 1, 2008; 181(1): 126 - 135. [Abstract] [Full Text] [PDF]
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M. Bonelli, A. Savitskaya, K. von Dalwigk, C. W. Steiner, D. Aletaha, J. S. Smolen, and C. Scheinecker Quantitative and qualitative deficiencies of regulatory T cells in patients with systemic lupus erythematosus (SLE) Int. Immunol., July 1, 2008; 20(7): 861 - 868. [Abstract] [Full Text] [PDF]
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M. Rifa'i, Z. Shi, S.-Y. Zhang, Y. H. Lee, H. Shiku, K.-i. Isobe, and H. Suzuki CD8+CD122+ regulatory T cells recognize activated T cells via conventional MHC class I-{alpha}{beta}TCR interaction and become IL-10-producing active regulatory cells Int. Immunol., July 1, 2008; 20(7): 937 - 947. [Abstract] [Full Text] [PDF]
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M. Poitrasson-Riviere, B. Bienvenu, A. Le Campion, C. Becourt, B. Martin, and B. Lucas Regulatory CD4+ T Cells Are Crucial for Preventing CD8+ T Cell-Mediated Autoimmunity J. Immunol., June 1, 2008; 180(11): 7294 - 7304. [Abstract] [Full Text] [PDF]
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H. Ebinuma, N. Nakamoto, Y. Li, D. A. Price, E. Gostick, B. L. Levine, J. Tobias, W. W. Kwok, and K.-M. Chang Identification and In Vitro Expansion of Functional Antigen-Specific CD25+ FoxP3+ Regulatory T Cells in Hepatitis C Virus Infection J. Virol., May 15, 2008; 82(10): 5043 - 5053. [Abstract] [Full Text] [PDF]
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L. Zheng, R. Sharma, J. T. Kung, U. S. Deshmukh, W. N. Jarjour, S. M. Fu, and S.-T. Ju Pervasive and stochastic changes in the TCR repertoire of regulatory T-cell-deficient mice Int. Immunol., April 1, 2008; 20(4): 517 - 523. [Abstract] [Full Text] [PDF]
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L. C. Ndhlovu, C. P. Loo, G. Spotts, D. F. Nixon, and F. M. Hecht FOXP3 expressing CD127lo CD4+ T cells inversely correlate with CD38+ CD8+ T cell activation levels in primary HIV-1 infection J. Leukoc. Biol., February 1, 2008; 83(2): 254 - 262. [Abstract] [Full Text] [PDF]
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M. Li, X. Zhang, X. Zheng, D. Lian, Z.-X. Zhang, H. Sun, M. Suzuki, C. Vladau, X. Huang, X. Xia, et al. Tolerogenic dendritic cells transferring hyporesponsiveness and synergizing T regulatory cells in transplant tolerance Int. Immunol., February 1, 2008; 20(2): 285 - 293. [Abstract] [Full Text] [PDF]
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J. Hanig and M. B. Lutz Suppression of Mature Dendritic Cell Function by Regulatory T Cells In Vivo Is Abrogated by CD40 Licensing J. Immunol., February 1, 2008; 180(3): 1405 - 1413. [Abstract] [Full Text] [PDF]
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A. K. Antons, R. Wang, K. Oswald-Richter, M. Tseng, C. W. Arendt, S. A. Kalams, and D. Unutmaz Naive Precursors of Human Regulatory T Cells Require FoxP3 for Suppression and Are Susceptible to HIV Infection J. Immunol., January 15, 2008; 180(2): 764 - 773. [Abstract] [Full Text] [PDF]
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J. Huan, L. J. Kaler, J. L. Mooney, S. Subramanian, C. Hopke, A. A. Vandenbark, E. F. Rosloniec, G. G. Burrows, and H. Offner MHC Class II Derived Recombinant T Cell Receptor Ligands Protect DBA/1LacJ Mice from Collagen-Induced Arthritis J. Immunol., January 15, 2008; 180(2): 1249 - 1257. [Abstract] [Full Text] [PDF]
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V. H. Nguyen, S. Shashidhar, D. S. Chang, L. Ho, N. Kambham, M. Bachmann, J. M. Brown, and R. S. Negrin The impact of regulatory T cells on T-cell immunity following hematopoietic cell transplantation Blood, January 15, 2008; 111(2): 945 - 953. [Abstract] [Full Text] [PDF]
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 M.-F. Liu, L.-H. Lin, C.-T. Weng, and M.-Y. Weng Decreased CD4+CD25+bright T cells in peripheral blood of patients with primary Sjogren's syndrome Lupus, January 1, 2008; 17(1): 34 - 39. [Abstract] [PDF]
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S. Li, E. J. Gowans, C. Chougnet, M. Plebanski, and U. Dittmer Natural Regulatory T Cells and Persistent Viral Infection J. Virol., January 1, 2008; 82(1): 21 - 30. [Full Text] [PDF]
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E. N. M. Nolte-'t Hoen, E. P. J. Boot, J. P. A. Wagenaar-Hilbers, J. H. M. van Bilsen, G. J. A. Arkesteijn, G. Storm, L. A. Everse, W. van Eden, and M. H. M. Wauben Identification and monitoring of effector and regulatory T cells during experimental arthritis based on differential expression of CD25 and CD134 J. Leukoc. Biol., January 1, 2008; 83(1): 112 - 121. [Abstract] [Full Text] [PDF]
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C. Siewert, U. Lauer, S. Cording, T. Bopp, E. Schmitt, A. Hamann, and J. Huehn Experience-Driven Development: Effector/Memory-Like {alpha}E+Foxp3+ Regulatory T Cells Originate from Both Naive T Cells and Naturally Occurring Naive-Like Regulatory T Cells J. Immunol., January 1, 2008; 180(1): 146 - 155. [Abstract] [Full Text] [PDF]
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A. A. Hombach, D. Kofler, A. Hombach, G. Rappl, and H. Abken Effective Proliferation of Human Regulatory T Cells Requires a Strong Costimulatory CD28 Signal That Cannot Be Substituted by IL-2 J. Immunol., December 1, 2007; 179(11): 7924 - 7931. [Abstract] [Full Text] [PDF]
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J. E. Willoughby, P. S. Costello, R. H. Nicolas, N. J. Robinson, G. Stamp, F. Powrie, and R. Treisman Raf Signaling but not the ERK Effector SAP-1 Is Required for Regulatory T Cell Development J. Immunol., November 15, 2007; 179(10): 6836 - 6844. [Abstract] [Full Text] [PDF]
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A. D. Reynolds, R. Banerjee, J. Liu, H. E. Gendelman, and R. L. Mosley Neuroprotective activities of CD4+CD25+ regulatory T cells in an animal model of Parkinson's disease J. Leukoc. Biol., November 1, 2007; 82(5): 1083 - 1094. [Abstract] [Full Text] [PDF]
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A. Giorgini and A. Noble Blockade of chronic graft-versus-host disease by alloantigen-induced CD4+CD25+Foxp3+ regulatory T cells in nonlymphopenic hosts J. Leukoc. Biol., November 1, 2007; 82(5): 1053 - 1061. [Abstract] [Full Text] [PDF]
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E. T. Samy, C. A. Meyer, P. Caplazi, C. L. Langrish, J. M. Lora, H. Bluethmann, and S. L. Peng Cutting Edge: Modulation of Intestinal Autoimmunity and IL-2 Signaling by Sphingosine Kinase 2 Independent of Sphingosine 1-Phosphate J. Immunol., November 1, 2007; 179(9): 5644 - 5648. [Abstract] [Full Text] [PDF]
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R. Sutmuller, A. Garritsen, and G. J Adema Regulatory T cells and toll-like receptors: regulating the regulators Ann Rheum Dis, November 1, 2007; 66(suppl_3): iii91 - iii95. [Abstract] [Full Text] [PDF]
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 H. Ben-David, A. Sharabi, M. Dayan, M. Sela, and E. Mozes The role of CD8+CD28 regulatory cells in suppressing myasthenia gravis-associated responses by a dual altered peptide ligand PNAS, October 30, 2007; 104(44): 17459 - 17464. [Abstract] [Full Text] [PDF]
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P. B. Silver, R. K. Agarwal, S.-B. Su, I. Suffia, R. S. Grajewski, D. Luger, C.-C. Chan, R. M. Mahdi, J. M. Nickerson, and R. R. Caspi Hydrodynamic Vaccination with DNA Encoding an Immunologically Privileged Retinal Antigen Protects from Autoimmunity through Induction of Regulatory T Cells J. Immunol., October 15, 2007; 179(8): 5146 - 5158. [Abstract] [Full Text] [PDF]
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R. Li, N. Perez, S. Karumuthil-Melethil, B. S. Prabhakar, M. J. Holterman, and C. Vasu Enhanced Engagement of CTLA-4 Induces Antigen-Specific CD4+CD25+Foxp3+ and CD4+CD25 TGF-beta1+ Adaptive Regulatory T Cells J. Immunol., October 15, 2007; 179(8): 5191 - 5203. [Abstract] [Full Text] [PDF]
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N. Fazilleau, H. Bachelez, M.-L. Gougeon, and M. Viguier Cutting Edge: Size and Diversity of CD4+CD25high Foxp3+ Regulatory T Cell Repertoire in Humans: Evidence for Similarities and Partial Overlapping with CD4+CD25 T Cells J. Immunol., September 15, 2007; 179(6): 3412 - 3416. [Abstract] [Full Text] [PDF]
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N. Hyka-Nouspikel, L. Lucian, E. Murphy, T. McClanahan, and J. H. Phillips DAP10 Deficiency Breaks the Immune Tolerance against Transplantable Syngeneic Melanoma J. Immunol., September 15, 2007; 179(6): 3763 - 3771. [Abstract] [Full Text] [PDF]
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J. A. Kapp, K. Honjo, L. M. Kapp, K. Goldsmith, and R. P. Bucy Antigen, in the Presence of TGF-beta, Induces Up-Regulation of FoxP3gfp+ in CD4+ TCR Transgenic T Cells That Mediate Linked Suppression of CD8+ T Cell Responses J. Immunol., August 15, 2007; 179(4): 2105 - 2114. [Abstract] [Full Text] [PDF]
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K. N. Taylor, V. R. Shinde-Patil, E. Cohick, and Y. L. Colson Induction of FoxP3+CD4+25+ Regulatory T Cells Following Hemopoietic Stem Cell Transplantation: Role of Bone Marrow-Derived Facilitating Cells J. Immunol., August 15, 2007; 179(4): 2153 - 2162. [Abstract] [Full Text] [PDF]
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 Y. Kato, K. Yoshimura, T. Shin, H. Verheul, H. Hammers, T. B. Sanni, B. C. Salumbides, K. Van Erp, R. Schulick, and R. Pili Synergistic In vivo Antitumor Effect of the Histone Deacetylase Inhibitor MS-275 in Combination with Interleukin 2 in a Murine Model of Renal Cell Carcinoma Clin. Cancer Res., August 1, 2007; 13(15): 4538 - 4546. [Abstract] [Full Text] [PDF]
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 F. H. Amante, A. C. Stanley, L. M. Randall, Y. Zhou, A. Haque, K. McSweeney, A. P. Waters, C. J. Janse, M. F. Good, G. R. Hill, et al. A Role for Natural Regulatory T Cells in the Pathogenesis of Experimental Cerebral Malaria Am. J. Pathol., August 1, 2007; 171(2): 548 - 559. [Abstract] [Full Text] [PDF]
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G. L. Stephens, J. Andersson, and E. M. Shevach Distinct Subsets of FoxP3+ Regulatory T Cells Participate in the Control of Immune Responses J. Immunol., June 1, 2007; 178(11): 6901 - 6911. [Abstract] [Full Text] [PDF]
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A. Demirkiran, B. M. Bosma, A. Kok, C. C. Baan, H. J. Metselaar, J. N. M. IJzermans, H. W. Tilanus, J. Kwekkeboom, and L. J. W. van der Laan Allosuppressive Donor CD4+CD25+ Regulatory T Cells Detach from the Graft and Circulate in Recipients after Liver Transplantation J. Immunol., May 15, 2007; 178(10): 6066 - 6072. [Abstract] [Full Text] [PDF]
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S. Makita, T. Kanai, Y. Nemoto, T. Totsuka, R. Okamoto, K. Tsuchiya, M. Yamamoto, H. Kiyono, and M. Watanabe Intestinal Lamina Propria Retaining CD4+CD25+ Regulatory T Cells Is A Suppressive Site of Intestinal Inflammation J. Immunol., April 15, 2007; 178(8): 4937 - 4946. [Abstract] [Full Text] [PDF]
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 I L Huibregtse, A U van Lent, and S J H van Deventer Immunopathogenesis of IBD: insufficient suppressor function in the gut? Gut, April 1, 2007; 56(4): 584 - 592. [Full Text] [PDF]
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J. Andersson, I. Stefanova, G. L. Stephens, and E. M. Shevach CD4+CD25+ regulatory T cells are activated in vivo by recognition of self Int. Immunol., April 1, 2007; 19(4): 557 - 566. [Abstract] [Full Text] [PDF]
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J. Bayry, F. Triebel, S. V. Kaveri, and D. F. Tough Human Dendritic Cells Acquire a Semimature Phenotype and Lymph Node Homing Potential through Interaction with CD4+CD25+ Regulatory T Cells J. Immunol., April 1, 2007; 178(7): 4184 - 4193. [Abstract] [Full Text] [PDF]
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A. Berhanu, J. Huang, S. C. Watkins, H. Okada, and W. J. Storkus Treatment-Enhanced CD4+Foxp3+ Glucocorticoid-Induced TNF Receptor Family RelatedHigh Regulatory Tumor-Infiltrating T Cells Limit the Effectiveness of Cytokine-Based Immunotherapy J. Immunol., March 15, 2007; 178(6): 3400 - 3408. [Abstract] [Full Text] [PDF]
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M. S. Turner, P. A. Cohen, and O. J. Finn Lack of Effective MUC1 Tumor Antigen-Specific Immunity in MUC1-Transgenic Mice Results from a Th/T Regulatory Cell Imbalance That Can Be Corrected by Adoptive Transfer of Wild-Type Th Cells J. Immunol., March 1, 2007; 178(5): 2787 - 2793. [Abstract] [Full Text] [PDF]
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M. Elrefaei, F. L. Ventura, C. A. R. Baker, R. Clark, D. R. Bangsberg, and H. Cao HIV-Specific IL-10-Positive CD8+ T Cells Suppress Cytolysis and IL-2 Production by CD8+ T Cells J. Immunol., March 1, 2007; 178(5): 3265 - 3271. [Abstract] [Full Text] [PDF]
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X. Luo, K. V. Tarbell, H. Yang, K. Pothoven, S. L. Bailey, R. Ding, R. M. Steinman, and M. Suthanthiran Dendritic cells with TGF-beta1 differentiate naive CD4+CD25- T cells into islet-protective Foxp3+ regulatory T cells PNAS, February 20, 2007; 104(8): 2821 - 2826. [Abstract] [Full Text] [PDF]
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 F. Marangoni, S. Trifari, S. Scaramuzza, C. Panaroni, S. Martino, L. D. Notarangelo, Z. Baz, A. Metin, F. Cattaneo, A. Villa, et al. WASP regulates suppressor activity of human and murine CD4+CD25+FOXP3+ natural regulatory T cells J. Exp. Med., February 19, 2007; 204(2): 369 - 380. [Abstract] [Full Text] [PDF]
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 C. Fozza, E. Nadal, M. Longinotti, and F. Dazzi T-cell receptor repertoire usage after allografting differs between CD4+CD25+ regulatory T cells and their CD4+CD25 counterpart Haematologica, February 1, 2007; 92(2): 206 - 214. [Abstract] [Full Text] [PDF]
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D. Golshayan, S. Jiang, J. Tsang, M. I. Garin, C. Mottet, and R. I. Lechler In vitro-expanded donor alloantigen-specific CD4+CD25+ regulatory T cells promote experimental transplantation tolerance Blood, January 15, 2007; 109(2): 827 - 835. [Abstract] [Full Text] [PDF]
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M. Kallikourdis, K. G. Andersen, K. A. Welch, and A. G. Betz Alloantigen-enhanced accumulation of CCR5+ 'effector' regulatory T cells in the gravid uterus PNAS, January 9, 2007; 104(2): 594 - 599. [Abstract] [Full Text] [PDF]
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 H Keino, M Takeuchi, Y Usui, T Hattori, N Yamakawa, T Kezuka, J-I Sakai, and M Usui Supplementation of CD4+CD25+ regulatory T cells suppresses experimental autoimmune uveoretinitis Br J Ophthalmol, January 1, 2007; 91(1): 105 - 110. [Abstract] [Full Text] [PDF]
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J. A. Kapp, K. Honjo, L. M. Kapp, X. y. Xu, A. Cozier, and R. P. Bucy TCR transgenic CD8+ T cells activated in the presence of TGF{beta} express FoxP3 and mediate linked suppression of primary immune responses and cardiac allograft rejection Int. Immunol., November 1, 2006; 18(11): 1549 - 1562. [Abstract] [Full Text] [PDF]
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M. Bodas, N. Jain, A. Awasthi, S. Martin, R. K. Penke Loka, D. Dandekar, D. Mitra, and B. Saha Inhibition of IL-2 Induced IL-10 Production as a Principle of Phase-Specific Immunotherapy J. Immunol., October 1, 2006; 177(7): 4636 - 4643. [Abstract] [Full Text] [PDF]
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L. Melencio, R. J. McKallip, H. Guan, R. Ramakrishnan, R. Jain, P. S. Nagarkatti, and M. Nagarkatti Role of CD4+CD25+ T regulatory cells in IL-2-induced vascular leak Int. Immunol., October 1, 2006; 18(10): 1461 - 1471. [Abstract] [Full Text] [PDF]
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A. Toda and C. A. Piccirillo Development and function of naturally occurring CD4+CD25+ regulatory T cells J. Leukoc. Biol., September 1, 2006; 80(3): 458 - 470. [Abstract] [Full Text] [PDF]
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F. Billiard, E. Litvinova, D. Saadoun, F. Djelti, D. Klatzmann, J. L. Cohen, G. Marodon, and B. L. Salomon Regulatory and Effector T Cell Activation Levels Are Prime Determinants of In Vivo Immune Regulation J. Immunol., August 15, 2006; 177(4): 2167 - 2174. [Abstract] [Full Text] [PDF]
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S. Wei, I. Kryczek, and W. Zou Regulatory T-cell compartmentalization and trafficking Blood, July 15, 2006; 108(2): 426 - 431. [Abstract] [Full Text] [PDF]
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J. Y.-S. Tsang, N. O. S. Camara, E. Eren, H. Schneider, C. Rudd, G. Lombardi, and R. Lechler Altered proximal T cell receptor (TCR) signaling in human CD4+CD25+ regulatory T cells J. Leukoc. Biol., July 1, 2006; 80(1): 145 - 151. [Abstract] [Full Text] [PDF]
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M. Mahic, S. Yaqub, C. C. Johansson, K. Tasken, and E. M. Aandahl FOXP3+CD4+CD25+ Adaptive Regulatory T Cells Express Cyclooxygenase-2 and Suppress Effector T Cells by a Prostaglandin E2-Dependent Mechanism J. Immunol., July 1, 2006; 177(1): 246 - 254. [Abstract] [Full Text] [PDF]
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K. Wing, Z. Fehervari, and S. Sakaguchi Emerging possibilities in the development and function of regulatory T cells Int. Immunol., July 1, 2006; 18(7): 991 - 1000. [Abstract] [Full Text] [PDF]
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H.-Y. Qin, R. Mukherjee, E. Lee-Chan, C. Ewen, R. C. Bleackley, and B. Singh A novel mechanism of regulatory T cell-mediated down-regulation of autoimmunity Int. Immunol., July 1, 2006; 18(7): 1001 - 1015. [Abstract] [Full Text] [PDF]
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H. Inaba and T. L. Geiger Defective cell cycle induction by IL-2 in naive T-cells antigen stimulated in the presence of refractory T-lymphocytes Int. Immunol., July 1, 2006; 18(7): 1043 - 1054. [Abstract] [Full Text] [PDF]
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A. Noble, A. Giorgini, and J. A. Leggat Cytokine-induced IL-10-secreting CD8 T cells represent a phenotypically distinct suppressor T-cell lineage Blood, June 1, 2006; 107(11): 4475 - 4483. [Abstract] [Full Text] [PDF]
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T. L. Vanasek, S. L. Nandiwada, M. K. Jenkins, and D. L. Mueller CD25+Foxp3+ Regulatory T Cells Facilitate CD4+ T Cell Clonal Anergy Induction during the Recovery from Lymphopenia J. Immunol., May 15, 2006; 176(10): 5880 - 5889. [Abstract] [Full Text] [PDF]
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H. Nishikawa, F. Qian, T. Tsuji, G. Ritter, L. J. Old, S. Gnjatic, and K. Odunsi Influence of CD4+CD25+ Regulatory T Cells on Low/High-Avidity CD4+ T Cells following Peptide Vaccination J. Immunol., May 15, 2006; 176(10): 6340 - 6346. [Abstract] [Full Text] [PDF]
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M. Beyer, M. Kochanek, T. Giese, E. Endl, M. R. Weihrauch, P. A. Knolle, S. Classen, and J. L. Schultze In vivo peripheral expansion of naive CD4+CD25high FoxP3+ regulatory T cells in patients with multiple myeloma Blood, May 15, 2006; 107(10): 3940 - 3949. [Abstract] [Full Text] [PDF]
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D.-M. Zhao, A. M. Thornton, R. J. DiPaolo, and E. M. Shevach Activated CD4+CD25+ T cells selectively kill B lymphocytes Blood, May 15, 2006; 107(10): 3925 - 3932. [Abstract] [Full Text] [PDF]
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M. Gad, D. Lundsgaard, S. Kjellev, N. N Kristensen, T. Seremet, P. t. Straten, and M. H Claesson Reactivity of naive CD4+CD25- T cells against gut microflora in healthy mice Int. Immunol., May 1, 2006; 18(5): 817 - 825. [Abstract] [Full Text] [PDF]
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J. J. A. Coenen, H. J. P. M. Koenen, E. van Rijssen, L. Boon, I. Joosten, and L. B. Hilbrands CTLA-4 Engagement and Regulatory CD4+CD25+ T Cells Independently Control CD8+-Mediated Responses under Costimulation Blockade J. Immunol., May 1, 2006; 176(9): 5240 - 5246. [Abstract] [Full Text] [PDF]
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R. Houot, I. Perrot, E. Garcia, I. Durand, and S. Lebecque Human CD4+CD25high Regulatory T Cells Modulate Myeloid but Not Plasmacytoid Dendritic Cells Activation J. Immunol., May 1, 2006; 176(9): 5293 - 5298. [Abstract] [Full Text] [PDF]
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K. S. Nicolson, E. J. O'Neill, A. Sundstedt, H. B. Streeter, S. Minaee, and D. C. Wraith Antigen-Induced IL-10+ Regulatory T Cells Are Independent of CD25+ Regulatory Cells for Their Growth, Differentiation, and Function J. Immunol., May 1, 2006; 176(9): 5329 - 5337. [Abstract] [Full Text] [PDF]
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) or absence (
) of
CD4+CD25+ cells (2.5 x
104).
