| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
+ T Cells1
Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
-chain knockout (KO) recipients of a
myelin oligodendrocyte glycoprotein p35–55 encephalitogenic T cell
line failed to recover from the acute phase of passive EAE. In
comparison with wild-type mice, active disease was more severe in
2-microglobulin KO mice. Reconstitution of TCR -chain
KO mice with wild-type spleen cells halted progression of disease and
favored recovery. Spleen cells from T cell-deficient mice, IL-7R KO
mice, or IFN-
KO mice were ineffective in this regard. Irradiation
or treatment of wild-type spleen cell population with anti-NK1.1
mAb before transfer abrogated the protective effect. Removal of
DX5+ cells from wild-type spleen cells by anti-DX5
Ab-coated magnetic beads before reconstitution abrogated the
suppressive properties of the spleen cells. TCR-deficient recipients of
the enriched DX5+ cell population recovered normally from
passively induced acute disease. DX5+ cells were sorted by
FACS into DX5+ 
TCR+ and DX5+
TCR- populations. Only recipients of the former
recovered normally from clinical disease. These results indicate that
recovery from acute EAE is an active process that requires
NK1.1+, DX5+ + TCR spleen
cells and IFN-. |
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Although the clinical course of disease varies from one inbred mouse strain to another, it typically consists of an acute phase followed by a recovery phase and then a number of relapses and remissions. The recovery phases may be complete as typified by the female SJL mouse model, or partial as seen with male B6 mice. At present, the mechanisms involved in regulation of the encephalitogenic response have not been well worked out. Although epitope spreading is hypothesized to be responsible for relapses (3, 4, 5, 6), the factors involved in recovery from the disease phases have been difficult to define. Mechanisms thought to play a role in recovery include apoptosis of effector T cells in the CNS, suppressive cytokines, immune deviation, and NK cells (7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18).
B6 TCR -chain knockout (KO) recipients of a MOG p35–55
encephalitogenic T cell line failed to recover from the acute phase of
passive EAE (19). Disease was progressive and frequently,
but not always, resulted in death. Wild-type B6 mice normally recovered
partially from acute disease followed by one or more mild relapses.
This finding indicates a requirement for one or more populations of
cells that express TCR for recovery from disease.
To assess the role played by different cell types, mice with targeted mutations of the immune system and transgenic (Tg) animals were assessed for susceptibility to active and/or passive EAE. TCR KO mice were reconstituted with normal wild-type spleen cells, spleen cells from various KO mutants, or wild-type spleen cells that had been irradiated or treated with mAbs specific for NK1.1 to test the hypothesis that NK1.1+ and/or NK1.1+ T cells play a role in recovery from the disease state.
NK1.1+ T cells are heterogeneous based on thymic
requirements for differentiation and tissue distribution (20, 21). The subpopulations differ phenotypically and are
distributed in a tissue-specific manner. Type I
NK1.1+ T cells are dependent on thymic expression
of CD1d for development, display a restricted T cell repertoire biased
strongly toward V8 and a canonical V14-J281 -chain, and are
found predominantly in the thymus and liver. Type II
NK1.1+ T cells develop independently of CD1d,
have a diverse T cell repertoire, and are found predominantly in the
spleen and bone marrow. Thymus and liver type I NK T cells express
moderate to low levels of a NK subpopulation marker, DX5, while spleen
and bone marrow NK T cells express higher levels of this marker. In
general, the expression level of DX5 is lower on CD4 T cells than on
double-negative or CD8 T cells (21).
Because DX5+ cells are present in higher numbers
in the spleen, it was of interest to determine whether this subset of
cells was involved in regulation of EAE. To assess the role played by
the DX5+ NK1.1+ cell
population in recovery from EAE, magnetic beads coated with
DX5-specific mAb were used to remove this cell population from a total
normal spleen cell population. The DX5-depleted spleen cells were then
used to reconstitute TCR-deficient mice following transfer of an
encephalitogenic T cell line. DX5+ cells
recovered from the magnet were used to reconstitute a second group of
mice. The results reported below indicate that the suppressive cells
are NK 1.1+ and DX 5+, are
radiosensitive, and are absent in T cell-deficient mice, implying that
the NK T cell population may play an important role in recovery from
disease. Recovery was also IFN- dependent, as active and passive
disease was more severe in IFN- KO mice.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Male C57BL/6J (B6),
C57BL/6J-2mtm1Unc
(2-microglobulin (2m)
KO), and C57BL/6J-Ifngtm1Ts (IFN- KO)
mice were obtained from The Jackson Laboratory (Bar Harbor, ME) and
housed in microisolator cages in the Animal Resource Center of the
Medical College of Wisconsin. C57BL/6 IL-7R KO mice were the kind gift
of Dr. Elizabeth Tivol of the Blood Research Institute of the Blood
Center of Southeastern Wisconsin, Milwaukee. Mice were used between 8
and 12 wk of age. TCR-/- (TCR KO) breeder
mice were purchased from The Jackson Laboratory, and animals were bred
in the Animal Resource Center. Mice were used at 7–9 wk of age. Groups
of four to five mice were used in each experiment. Each experiment was
repeated a minimum of two times. Male mice were used for all
experiments.
Antigens
MOG p35–55, M-E-V-G-W-Y-R-S-P-F-S-R-V-V-H-L-Y-R-N-G-K, was synthesized by the Protein and Nucleic Acid Facility of the Medical College of Wisconsin. For induction of active EAE, animals were immunized with 200 µg peptide and 50 µg killed Mycobacterium tuberculosis, H37RA emulsified in IFA. A total of 0.1 ml of emulsion was injected into four sites on the flanks. At 0 and 48 h following the initial injections, 400 ng of B. pertussis toxin (Sigma, St. Louis, MO) was administered i.p.
Generation of T cell lines
Ten days following immunization, the draining lymph nodes were removed, and a single cell suspension was prepared and cultured without further separation at 3 x 106/ml, 2 ml/well, in 24-well tissue culture plates. Culture media were RPMI 1640 supplemented with 10% FCS, 5 x 10-5M 2-ME, 100 U/ml penicillin, 100 µg/ml streptomycin, 2 mM L-glutamine, and 10 mM HEPES buffer; 10 µg/ml p35–55; and 10% Con A supernatant from a rat spleen cell culture as a source of lymphokines. After 4 days at 37oC, blast cells were isolated on a Ficoll-Hypaque gradient, resuspended at 2 x 105/ml with irradiated (3000 rad) syngeneic spleen cells at 1 x 106/ml. Erythrocytes in spleen cell preparations were lysed with ammonium chloride. Cells were cultured in the absence of nominal Ag in tissue culture flasks for a 10-day rest period, followed by a 4-day restimulation period during which the surviving cells were cultured at 1 x 105/ml with p35–55 (10 µg/ml) and fresh irradiated syngeneic spleen cells at 2.5 x 106/ml in 24-well culture plates. Passive EAE was induced in irradiated (500 rad) syngeneic male mice by transfer of the indicated number of activated T cell blasts. Mice were examined daily for clinical signs of EAE and were graded on a scale of 0–4, as described previously (2). Mice that remained at grade 4 for more than 1 day were euthanized.
Antibodies
B cell hybridomas secreting monoclonal anti-NK1.1, PK 136,
and monoclonal anti-CD3, 145-2C11, were obtained from the American
Type Culture Collection (Manassas, VA). They were propagated in Protein
Free Hybridoma Medium from Life Technologies Life Sciences (Rockville,
MD). The following fluorochrome-labeled Abs were purchased from
PharMingen (San Diego, CA): anti-CD3 (145-2C11), anti CD4 (GK1.5),
anti-CD8 (53-6.7), anti-CD25 (7D4), anti-NK1.1 (PK136),
anti-NK (DX5), and anti-TCR (H57-597). Fc Block (2.4G2)
was used according to the manufacturer’s instructions to inhibit
nonspecific binding of labeled Abs to FcR on immune cells.
Spleen cells
Spleens were removed from normal wild-type or mutant mice, and a single cell suspension was prepared and treated to remove erythrocytes. A total of 5 x 107 cells was infused into T cell-deficient animals either at the time of transfer of the encephalitogenic T cell line or just before the appearance of disease signs. Similar results were found regardless of the time of reconstitution. To assess the effect of irradiation, wild-type mice were irradiated (500 rad), spleens removed, and a single cell suspension prepared as above. To remove NK1.1+ cells, a single cell suspension was prepared from normal spleen, and the cell concentration adjusted to 1 x 107 cells/ml in RPMI 1640 supplemented with 0.3% BSA. To the suspension was added affinity-purified mAb PK 136 or a culture supernatant of 145-2C11, and the mixture incubated for 60 min at 4oC. At the end of the incubation period, the cells were centrifuged and then resuspended in RPMI 1640/0.3% BSA and Low-Tox rabbit complement (Accurate Chemical and Scientific Company, Westbury, NY). After 60 min at 37oC, the cells were washed by centrifugation, and a sample removed for staining with trypan blue. For separation of DX5+ cells from the spleen cell preparations, 1 x 108 spleen cells were incubated with 100 µl of anti-NK (DX5) microbeads (Miltenyi Biotec, Auburn, CA) for 15 min at 4oC. The cells were then washed and the suspension passed through a MS mini column in the presence of a magnetic field in a MACS separator. DX5- cells were allowed to pass through the column, and then the magnet was removed and the DX5+ cells were eluted from the column.
Flow cytometry
One million cells were washed once with PBS/1%FBS/0.4% sodium
azide and then incubated with Fc Block (PharMingen) for 15 min at
4oC. The suspension was then centrifuged and the
pellet resuspended in 30 µl of PBS/3% BSA, following which 1.5 µl
of labeled Ab was added to the suspension. After 30 min at
4oC, the suspension was washed three times with
PBS/1%FBS/0.4% sodium azide, and the cells analyzed by flow
cytometry. The gates were set by incubation of spleen cells from each
strain with labeled isotype control irrelevant Abs. Sorting of
DX5+ TCR+ and
DX5+ TCR- cells was
done by incubation of DX5 cells isolated by magnetic cell sorting with
FITC-labeled H57-597 anti-TCR -chain mAb (BD PharMingen, San
Diego, CA). The washed cells were sorted using a
FACStarPlus from Becton Dickinson Immunocytometry
Systems (Mountain View, CA) with CellQuest software.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Fig. 1
shows the results of an experiment
in which 1.5 x 106 encephalitogenic T cells
were adoptively transferred into TCR KO mice. Either at the time of
transfer or 10 days after transfer of the encephalitogenic T cells,
5 x 107 spleen cells from wild-type mice
were adoptively transferred to the TCR KO recipients. As a positive
control, a group of wild-type B6 recipients of the encephalitogenic T
cell line was included in the experiment. The unmanipulated TCR KO
recipients rapidly progressed to death. TCR KO recipients reconstituted
with wild-type spleen cells either at the time of transfer or 10 days
after transfer recovered with the same kinetics as wild-type controls.
These findings indicated that a TCR+ cell
was involved in recovery from clinical disease, and that reconstitution
with normal spleen cells could be done either at the time of transfer
of the encephalitogenic line or at the onset of clinical signs. For the
remainder of the study, spleen cell reconstitution was done at the
onset of clinical signs.
|
).
|
, this treatment
completely abrogated the suppressive properties of the wild-type spleen
cells, indicating the regulatory population was
NK1.1+. This finding coupled with the results in
T cell-deficient mice (Fig. 1
) indicated that the regulatory population
might, at least in part, be found in the NKT cell subpopulation.
|
2m KO mice;
thus, this mutant strain has been reported to be NKT cell deficient
(22, 23). NK cells, in contrast, are found at normal
levels in 2m KO mice. The hypothesis that NKT
cells play a role in regulation was tested by active immunization of
2m-deficient mice or use of spleen cells from
these mice to reconstitute TCR KO animals. IL-7R KO mice also lack NKT
cells, but have normal levels of NK cells, providing a second strain in
which to test the above hypothesis. Before these experiments, the
levels of NK and NKT cells in these two mutant strains were assessed by
flow cytometry. Spleen cells from 2m KO mice
contained 1% NKT and 5.2% NK cells, while spleen cells from IL-7R KO
mice contained 0.4% NKT and 13.9% NK cells. Repeated analyses
indicated that NKT cells in 2m KO mice were
present in greatly reduced numbers, while NKT cells were absent from
IL-7R mice. Spleens of wild-type B6 mice contained 
4% NKT
cells.
The results of one of two experiments in which B6 wild-type mice or
2m-KO mice were actively immunized with MOG
p35–55 are shown in Fig. 4A.
In each experiment, acute disease was more severe and recovery less
apparent in the mutant mice as compared with the wild-type animals. To
determine whether this effect was a function of the spleen cell
population, encephalitogenic T cells were adoptively transferred to TCR
KO mice. At the time of disease onset, 5 x
107 spleen cells from wild-type or
2m-KO mice were adoptively transferred to the
T cell-deficient recipients. As found previously, the recipients of
wild-type spleen cells recovered normally, whereas the recipients of
the spleen cells from the 2m-KO mice recovered
partially (Fig. 4B). Interestingly, the disease severity in
the mutant mice was intermediate between unmanipulated TCR KO mice and
mice reconstituted with wild-type spleen cells. This may be due to the
low level of residual NKT cells in the 2m-KO
mice. These findings, which are consistent with the results of active
immunization, indicate a role for NK T cells in the regulation of
clinical EAE.
|
). Only the recipients of the
wild-type spleen cells recovered normally from clinical disease, again
implicating NK T cells as having a role in regulation of clinical
disease.
|
in recovery from
clinical signs of EAE, TCR KO recipients of the encephalitogenic T cell
line were reconstituted with 5 x 107 spleen
cells from IFN- KO mice. The recipients of the mutant cells did not
recover from disease, indicating a requirement for this cytokine in the
recovery process (Fig. 6). Phenotypic
analysis of the spleen cell population of the IFN- KO mice by flow
cytometry showed levels of NK and NKT cells similar to those in
wild-type mice.
|
Flow cytometric analysis of the DX5-depleted and DX5-enriched cell
populations is shown in Fig. 7. Very few
DX5+ cells were found in the flow-through
(DX5-depleted) fraction. Double staining of the flow-through fraction
with anti-NK1.1 and anti-CD3 mAbs revealed that 29.7% of the
cells were CD3 single positive, 1.5% of the cells were double positive
for CD3 and NK1.1, and 1.3% of the cells were single positive for
NK1.1. Approximately one-half of the cells in the eluted fraction
stained with DX5 mAb. This is most likely an underestimate, as the
anti-DX5 beads had not been removed from the eluted cells. Double
staining of the latter population with DX5 and anti-TCR mAbs
revealed that 22% of the cells were DX5+
TCR+ and 78% were DX
5+ TCR-.
|
), indicating that this subpopulation
was essential in regulation of the encephalitogenic response.
DX5+ cells isolated from TCR -chain KO mice
were completely ineffective in inducing recovery, implicating
DX5+ + T cells as the
effectors.
|
). As shown in Fig. 10, only recipients of the
DX5+ TCR+ population
recovered normally from clinical disease, confirming that
DX5+ TCR+ cells were
necessary and sufficient for recovery from acute EAE.
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
-chain KO mice and B6
RAG-1 KO mice failed to recover following adoptive transfer of an
encephalitogenic T cell line, indicating a regulatory deficiency
related to a lack of T cells in the mutant mice. Reconstitution of the
T cell-deficient mice with 5 x 107 spleen
cells from normal wild-type mice, but not TCR-deficient mice, restored
the regulatory activity to normal (19). Removal of
DX5+ cells from the spleen cell population before
reconstitution abrogated suppressive activity, thus eliminating B cells
and the great majority of T cells as having an essential role in
recovery from acute disease.
Mice transgenic for a TCR from an encephalitogenic MBP-specific T cell
clone (MBP/TCR Tg) provide an interesting parallel to the above
results. In the Tg mice, the majority of the peripheral T cells
expressed a TCR derived from an encephalitogenic T cell clone; however,
spontaneous EAE was not universally observed when the mice were kept in
a pathogen-free environment (24). It was found that the
incidence of spontaneous disease was inversely related to the
percentage of peripheral non-Tg T cells in the animals, as crossing the
Tg TCR onto a RAG-1 background resulted in a 100% incidence of
spontaneous EAE in the hybrid mice (25, 26). These
findings imply that TCR+ T cells were
important for regulatory function. These findings also indicate that NK
cells are not the regulatory population, as levels of NK cells in RAG-1
mice should be normal or even above normal.
To identify the regulatory cell population, lymphoid cells from various
KO strains of mice were infused into the Tg TCR/RAG-1 mice before onset
of symptoms. Lymphoid populations lacking B cells, 
T cells, and
CD8 T cells retained regulatory activity, as did spleen cells from
2m KO mice. Only a
+ T cell population possessed effective
regulatory activity. Additional studies have shown that the regulatory
cells that prevent spontaneous EAE in this model are
CD4+ T cells expressing a diverse T cell
repertoire (27).
NK1.1+ cells were implicated in regulation when
it was found that treatment of wild-type B6 mice with anti-NK1.1
mAb followed by immunization with MOG p35–55 resulted in EAE of
increased severity as compared with unmanipulated B6 mice
(18). In this study, immunization of
2m KO mice resulted in clinical disease
slightly more severe (maximum clinical grade of 1 for wild type and
2.5 for the KO mutants; Figs. 1 and 3, respectively) than was seen with
wild-type mice. This was further augmented by treatment with
anti-NK1.1 mAb, indicating a partial regulatory defect in the KO
mice, and that residual regulatory activity was due to
NK1.1+ cells. In contrast to the interpretation
of experiments with MBP/TCR Tg mice, these authors concluded that
regulatory activity was due to NK cells (18). It is
important to note that the two experimental models are quite different.
In the first instance, regulation of spontaneous disease in MBP/TCR Tg
mice was examined; in the latter, actively induced disease in wild-type
mice was tested.
In the above experiments, it was possible that either NK or NKT cells
or both were involved in the regulation of EAE.
2m KO mice have been reported to lack NKT
cells because they lack the restricting element, CD1d. However, it has
been recently published that the NK1.1+
TCR+ population is composed of at least two
subpopulations: one derived on thymic CD1d molecules and expressing a
restricted TCR repertoire with a canonical -chain, and a second
derived independently of CD1d and expressing a diverse TCR repertoire.
The former subpopulation was found more frequently in the thymus and
the liver, and the latter subpopulation was found more frequently in
the spleen and bone marrow. The epitope with which the mAb DX5 reacts
is predominantly restricted to CD1d-independent NKT cells found in the
spleen and bone marrow (20, 21).
It is unlikely that NK cells are the sole regulatory population, as
they are found at normal or increased levels in TCR KO mice, RAG-1 KO
mice, and IL-7R KO mice, mutant strains in which NKT cells are absent.
Passive EAE is more severe in these strains than in wild-type mice.
Significantly, disease severity is intermediate in
2m KO mice, a strain in which NKT cells are
present in reduced numbers. In light of these results, it is likely
that NKT cells are involved in regulatory activity either alone or in
concert with NK cells. In support of the latter speculation, it has
been found that in vivo activation of NK cells, as assessed by
production of IFN-, is dependent on the presence of an intact NKT
cell population. When wild-type B6 mice were stimulated by injection of
-GalCer, there was a very rapid increase in IFN- production by NK
cells and up-regulation of the activation marker, CD69. This effect was
absent in B6 RAG KO mice and CD1 KO mice, implying that activation of
NK cells in this system requires the presence of an intact NKT cell
population (28). In the same report, it was shown that
IFN- was required for the activation of NK cells by NKT cells.
The role of NK or NKT cells in the regulatory process is strengthened
by the findings that EAE in the absence of IFN- is more severe
(17, 29, 30). In the present study, spleen cells from
IFN- KO mice were less suppressive than wild-type cells when
administered to TCR KO recipients of the encephalitogenic T cell line.
NKT cells, when stimulated, are a rich source of IFN-. This cell
population also secretes large amounts of IL-4 upon stimulation. In
light of the current paradigm of recovery from EAE as a function of
immune deviation, it would be predicted that IL-4 would be critical for
recovery. In fact, active or passive EAE in IL-4 KO mice is not
significantly different from the disease in wild-type mice, indicating
that recovery proceeds normally in the absence of IL-4 (19, 31, 32).
NKT cells have been implicated as regulatory cells in a number of
experimental situations, including tumor immunity, autoimmune processes
such as type I diabetes, and bacterial infection (33, 34, 35, 36).
When stimulated through the TCR by anti-CD3, NKT cells are
producers of copious amounts of IL-4 (37, 38). Likewise,
when stimulated with IL-12, NKT cells secrete IFN-
(39). For this reason, it has been postulated that they
may play a central role in directing the immune response toward the Th1
or Th2 pathway during the primary immune response, although this
hypothesis has been questioned (40, 41). It seems unlikely
that immune deviation is playing a role in the regulatory process
described in this work, as recovery occurs very rapidly after
reconstitution with normal spleen cells. The kinetics of recovery would
be more in line with secretion of soluble factors that down-regulate
the encephalitogenic response by affecting a cell or cells critical to
maintenance of EAE.
We have also shown previously that nonactivated encephalitogenic T cells transferred into TCR KO mice caused EAE spontaneously. Transfer of the same T cells into wild-type mice was without effect (19). This implied active suppression of the encephalitogenic T cells in the wild-type mice. Suppression in these recipients was readily overcome by immunization with neuroantigen or by nonspecific activation of the immune system (42). We hypothesize that the regulatory population in wild-type mice exerts a weak suppressive effect on self-reactive T cells that keeps them in check under normal conditions, and that agents that affect the regulatory cells or are sufficiently potent activators of T cells can override this weak control.
In summary, these findings support a regulatory model in which NKT cells suppress the encephalitogenic response either directly or in concert with NK cells. The means by which suppression is achieved is under active investigation.
|
Footnotes |
|---|
2 Address correspondence and reprint requests to Dr. Robert B. Fritz, Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226.
3 Abbreviations used in this paper: EAE, experimental autoimmune encephalomyelitis; 2m, 2-microglobulin; KO, knockout; MBP, myelin basic protein; MOG, myelin oligodendrocyte glycoprotein; Tg, transgenic.
Received for publication June 13, 2000. Accepted for publication January 2, 2001.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
8.2+ T lymphocytes in the spinal cord during recovery from experimental autoimmune encephalomyelitis induced in Lewis rats by inoculation with myelin basic protein. J. Neurol. Sci. 139:1.
T lymphocytes in the nervous system in experimental autoimmune encephalomyelitis: its possible implications for recovery and acquired tolerance. J. Autoimmun. 5:401.[Medline]
8.2 chain are involved in the control of collagen II-induced arthritis and experimental autoimmune encephalomyelitis. J. Exp. Med. 185:1725.1 in experimental allergic encephalomyelitis. Int. Immunol. 4:615. plays a critical down-regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. J. Immunol. 157:3223.[Abstract]
/ T cell-deficient C57BL/6 mice. J. Neuroimmunol. 87:171.[Medline]
gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). J. Immunol. 156:5.[Abstract]
confers resistance to experimental allergic encephalomyelitis. Eur. J. Immunol. 26:1641.[Medline]
14+ NK T cells associated with disease development in autoimmune-prone mice. J. Immunol. 156:4035.[Abstract]
T cells in IL-12 production during Salmonella infection. J. Immunol. 163:2057./-T cell receptor (TCR)+Cd4-Cd8- (NKT) thymocytes prevent insulin-dependent diabetes mellitus in nonobese diabetic (Nod)/Lt mice by the influence of interleukin (IL)-4 and/or IL-10. J. Exp. Med. 187:1047.TCR+ CD4- CD8- T cell deficiency and IDDM in NOD/Lt mice. Diabetes 46:572.[Abstract]
2-Microglobulin-dependent NK1.1+ T cells are not essential for helper 2 immune responses. J. Exp. Med. 184:1295.This article has been cited by other articles:
|
|
 |
|
  R. Winkler-Pickett, H. A. Young, J. M. Cherry, J. Diehl, J. Wine, T. Back, W. E. Bere, A. T. Mason, and J. R. Ortaldo In Vivo Regulation of Experimental Autoimmune Encephalomyelitis by NK Cells: Alteration of Primary Adaptive Responses J. Immunol., April 1, 2008; 180(7): 4495 - 4506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Galazka, A. Jurewicz, W. Orlowski, M. Stasiolek, C. F. Brosnan, C. S. Raine, and K. Selmaj EAE Tolerance Induction with Hsp70-Peptide Complexes Depends on H60 and NKG2D Activity J. Immunol., October 1, 2007; 179(7): 4503 - 4512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Wiethe, M. Schiemann, D. Busch, L. Haeberle, M. Kopf, G. Schuler, and M. B. Lutz Interdependency of MHC Class II/Self-Peptide and CD1d/Self-Glycolipid Presentation by TNF-Matured Dendritic Cells for Protection from Autoimmunity J. Immunol., April 15, 2007; 178(8): 4908 - 4916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Duarte, M. Stenstrom, S. Campino, M.-L. Bergman, M. Lundholm, D. Holmberg, and S. L. Cardell Prevention of Diabetes in Nonobese Diabetic Mice Mediated by CD1d-Restricted Nonclassical NKT Cells J. Immunol., September 1, 2004; 173(5): 3112 - 3118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Teige, I. Teige, S. Lavasani, R. Bockermann, E. Mondoc, R. Holmdahl, and S. Issazadeh-Navikas CD1-Dependent Regulation of Chronic Central Nervous System Inflammation in Experimental Autoimmune Encephalomyelitis J. Immunol., January 1, 2004; 172(1): 186 - 194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yang, A. Ueno, M. Bao, Z. Wang, J. S. Im, S. Porcelli, and J.-W. Yoon Control of NKT Cell Differentiation by Tissue-Specific Microenvironments J. Immunol., December 1, 2003; 171(11): 5913 - 5920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. T. Mars, V. Laloux, K. Goude, S. Desbois, A. Saoudi, L. Van Kaer, H. Lassmann, A. Herbelin, A. Lehuen, and R. S. Liblau Cutting Edge: V{alpha}14-J{alpha}281 NKT Cells Naturally Regulate Experimental Autoimmune Encephalomyelitis in Nonobese Diabetic Mice J. Immunol., June 15, 2002; 168(12): 6007 - 6011. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. W. Jahng, I. Maricic, B. Pedersen, N. Burdin, O. Naidenko, M. Kronenberg, Y. Koezuka, and V. Kumar Activation of Natural Killer T Cells Potentiates or Prevents Experimental Autoimmune Encephalomyelitis J. Exp. Med., December 17, 2001; 194(12): 1789 - 1799. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
), B6
wild-type mice (
), B6 TCR KO recipients reconstituted with 5 x
107 wild-type spleen cells at time of transfer of
encephalitogenic T cells (
), and B6 TCR KO recipients reconstituted
with 5 x 107 wild-type spleen 10 days after transfer
of encephalitogenic T cells (
). Each mouse received 1.5 x
106 MOG p35–55-activated encephalitogenic T blasts i.v.
Groups of four mice were used for these experiments.
). Each mouse received 1.5 x
106 MOG p35–55-activated encephalitogenic B6 T blasts i.v.
p < 0.001 between DX5+
TCR+ and DX5+ TCR- groups.