| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
,,§
*
Committee on Immunology,
Gwen Knapp Center for Lupus and Immunology Research,
Department of Medicine, and
§
Howard Hughes Medical Institute, Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637; and
¶
University of Miami School of Medicine, Miami, FL 33136
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The TNF receptor (TNFR)3 family is a rapidly expanding group of related proteins which includes TNFR I and II, Fas, 4-1BB, OX40, CD27, CD40, and CD30 (5, 6). The members of the TNFR family are likely candidates as potential regulators of late stage T cell activation. For example, CD40 is a potent costimulatory receptor for B cell proliferation, differentiation, and survival (7, 8). Mechanistically, CD40 has been shown to prevent apoptosis through the induction of Bcl-xL (9, 10) and to promote cell-cycle progression by regulating cdk4 and cdk6 expression in a B cell line (9). The importance of CD40 in B cell physiology suggests that there may be a related family member(s) that could regulate T cell costimulation.
TNFR family members share significant homology in the extracellular
domains but limited homology in their intracellular domains (6).
However, investigation of the binding properties of the cytoplasmic
domains to intracellular proteins has demonstrated that there are also
important similarities in their intracellular domains. For example, the
cytoplasmic domain of CD30 has recently been shown to have
TNFR-associated factor (TRAF) binding domains with significant
similarity to the TRAF binding domains of CD40 (11). In both receptors
these domains have been shown to be necessary and sufficient for
NF-
B induction (12, 13, 14). In addition, CD30 and CD40 can augment
cytokine production by cell lines derived from Reed-Sternberg cells of
Hodgkin’s disease (15). These observations suggested that CD30 may
serve as a positive regulator of T cell function.
CD30 has been reported to augment proliferation in human T cells during a primary stimulation and in some cell lines derived from Hodgkin’s lymphoma, whereas in other cell lines of the same origin no effect has been observed (16, 17). CD30 signaling can also enhance cytokine production by a murine CTL line (18). In contrast, CD30-deficient mice have impaired negative selection of thymocytes (19). In addition, CD30 signaling can augment TCR-dependent apoptosis of a T cell hybridoma (20), and down-regulate CD28 expression and inhibit cytotoxicity of a large granular lymphoma cell line (21). Together these reports indicate that CD30 in some instances can promote cell survival and in others induce apoptosis. A similar dichotomy of function has been reported for other members of the TNFR family, such as TNFR II, and can perhaps be explained by the cellular context in which a signal is delivered (22, 23, 24).
It has been reported that CD30 expression on human and murine T cells is activation dependent (18, 25, 26). However, little is known about the exact stimuli that regulate CD30 expression. Here we report that CD30 expression on activated T cells requires costimulation via CD28 or the addition of IL-4 as an exogenous cytokine. CD28 induces CD30 expression through both IL-4-independent and IL-4-dependent mechanisms. In support of the hypothesis that CD30 may function as a positive regulator of T cell function, we also report that CD30 provides a costimulatory signal for T cell proliferation during a secondary stimulation.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
BALB/cJ mice and BALB/cJ IL-4-deficient mice were purchased from The Jackson Laboratories (Bar Harbor, ME). The CD28-deficient mice were generated as previously described (27). The CD28 null allele has subsequently been bred from the C57BL/6 background onto the BALB/cJ background. TCR transgenic mice specific for OVA peptide fragment 323–339 (DO11.10) and I-Ad restricted were initially provided as a generous gift from D. Loh (Washington Uuniversty, St. Louis, MO). Wild-type and CD28-deficient BALB/cJ mice carrying the DO11.10 transgene were generated by appropriate breeding. All mice were bred and maintained in a specific pathogen-free facility at the University of Chicago (Chicago, IL).
Cell culture
For all CD30 expression experiments, bulk lymph node cells were isolated and single cell suspensions were cultured in complete medium as previously described (28). The anti-CD3 stimulations were conducted in 48-well plates coated with a 1 µg/ml solution of anti-CD3 in 50 mM Tris (pH 9.4) with 2.5 x 105 cells/well. For the OVA TCR Tg experiments, 4 x 105 cells/well were cultured in 48-well plates with 100 µM OVA peptide 323–339. As indicated in the text and figure legends, additional reagents were added to the above conditions as follows: rIL-2 (100 U/ml, Boehringer Mannheim, Indianapolis, IN), rIL-4 (10,000 U/ml, R&D Systems, Minneapolis, MN), rIL-13 (50 ng/ml, R&D Systems), anti-CD28 (PV1, 10 µg/ml, kindly provided by C. June, Naval Medical Research Institute, Bethesda, MD), anti-IL-4 (11B11, 10 µg/ml, a gift from R. Coffman, DNAX Corp., South San Francisco, CA), anti-IL-13 (50 µg/ml, R&D Systems), and CTLA4-Ig (100 µg/ml, G. Gray, Genetics Institute, Cambridge, MA). This dose of CTLA4-Ig was chosen because it gave maximal inhibition of a one way mixed lymphocyte reaction. Anti-IL-13 was used at a dose that was two times greater than the dose necessary to achieve one-half maximal inhibition of 10 ng/ml of recombinant murine IL-13 as assayed using the factor-dependent cell line, TF-1.
Flow cytometry
Bulk lymph node cells from the indicated animals were harvested on day 5 of primary culture and stained with either a phycoerythrin (PE)-conjugated-hamster (anti-TNP; 2,4,6-trinitrophenol) Ig control, anti-CD30-PE, or anti-CD28-PE (37.51). In some instances two color staining was performed, using the described PE-conjugated Abs in combination with either FITC-coupled rat IgG2a isotype control or anti-Thy-1.2-FITC. All of the Abs used for the described FACS experiments were purchased from PharMingen (San Diego, CA). In all experiments 10,000 live events were acquired and positive staining with specific Ab was analyzed relative to the isotype control for the same culture condition using a FACScalibur flow cytometer and Cellquest software (Becton Dickinson, Mountain View, CA).
Proliferation assays
Bulk lymph node cells from BALB/c mice were cultured in 24-well plates coated with a 1 µg/ml anti-CD3 50 mM Tris (pH 9.4) solution at 1 x 106 cells/well. Where indicated, 10 µg/ml anti-CD28 was also added to the culture supernatant. After 5 days, cells were harvested from the plate, washed two times, and placed in fresh medium for 24 h in a 37°C incubator. For restimulation, cells were washed two more times, and 5 x 104 cells/well were stimulated in 96-well flat bottom microtiter plates with the indicated concentration immobilized anti-CD3, in wells coated with a 20 µg/ml anti-CD30 in a 50 mM Tris (pH 9.4) solution, as described by Bowen et al. (18), or 10 µg/ml soluble anti-CD28, or no additional stimulus. CD30 expression was determined at both the time of harvest and restimulation. Each well was pulsed with 1 µCi tritiated thymidine ([3H]TdR, ICN Biochemicals, Costa Mesa, CA) for the final 8 h of a 48-h culture. All plates were harvested using a Tomtec Mach II cell harvester and counted on a Betaplate liquid scintillation counter (Wallac Inc., Gaithersburg, MD). All results are expressed as the mean ± SD of triplicate cultures.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Previously, Bowen et al. (18) reported that splenic T cells
stimulated with anti-CD3 express CD30 at peak levels 4 to 6 days
following activation. To obtain a population of CD30-expressing T cells
for our studies, bulk lymph node T cells from wild-type mice were
stimulated in wells coated with a 1 µg/ml anti-CD3 solution, and
CD30 expression was analyzed. Although in some instances a small
population of T cells expressing CD30 was observed on day 5, CD30 was
not detectable on the majority of T cells using anti-CD3 stimulus
alone (Fig. 1
B, upper
panel). In fact, when T cells were cultured in wells coated
with as much as a 10 µg/ml anti-CD3 solution there was no
observable induction of CD30 expression (data not shown). This
suggested that CD30 was either expressed at levels below the detection
limit of flow cytometry or that an additional signal was required for
induction of CD30 expression on T cells. Therefore we tested whether
costimulation through CD28 could induce CD30 expression. Stimulation of
bulk lymph node cells with anti-CD3 in the presence of
anti-CD28 resulted in a uniform population of CD30 expressing
Thy-1.2+ cells after 5 days in culture (Fig. 1C,
upper panel). Anti-CD30 stained T cells were first
detected at 3 days following stimulation, and maximal CD30 expression
was reproducibly observed on day 5 (data not shown and Fig. 1C, upper panel).
|
B, lower panel). However after
treatment with anti-CD3 and anti-CD28, expression of CD28 was
dramatically reduced (Fig. 1C, lower
panel). This observation was not due to competition between
the anti-CD28 used for stimulation and the CD28 Ab used for flow
cytometry, because incubation of either a CD28-positive T cell
hybridoma or lymph node cells at 4°C with the CD28 Ab used for
stimulation did not block binding of the Ab used for FACS analysis
(data not shown). Thus, in vitro activation of T cells with
anti-CD3 and anti-CD28 results in expression of high levels of
CD30 and low levels of CD28. This result suggests that under the
culture conditions described here, chronic ligation of CD28 leads to
receptor down modulation from the T cell surface. It is possible that
CD30 serves to regulate the late function and/or differentiation of
this population of T cells and may potentially substitute for CD28
function in this context. CD30 can function as a costimulatory receptor during secondary T cell stimulation
To address the effects of CD30 signaling in T cells stimulated
with anti-CD3 and anti-CD28, we examined the effects of CD30
crosslinking during a secondary stimulation with anti-CD3. Bulk
lymph node cells were stimulated with anti-CD3 and anti-CD28
for 5 days. Cells were next washed to remove the residual anti-CD3
and anti-CD28 and cultured in medium alone for 24 h. The cells
were then restimulated in the presence of anti-CD3 alone or
anti-CD3 and anti-CD30 or anti-CD3 and anti-CD28. In
these experiments, the restimulated Thy-1.2+
population of cells was comprised of 
90% CD4+ of which
75% displayed a memory phenotype as defined by low Mel-14 mean
fluorescence (data not shown). Figure 2,
A and B, show that ligation of CD30 augments
proliferation of T cells in the presence of a suboptimal dose of
anti-CD3. Anti-CD30 also had a small effect in the absence of
additional anti-CD3; this effect may be due to synergy with
residual anti-CD3 from the primary culture. The costimulatory
effect of anti-CD30 is comparable to that of anti-CD28 (Fig. 2B). These data indicate that CD30 can deliver a
costimulatory signal to previously activated T cells.
|
To confirm the importance of CD28 in the induction of CD30
expression, wild-type and CD28-deficient OVA TCR Tg lymph node cells
were treated with 100 µM OVA peptide 323–339 for 5 days and analyzed
for CD30 expression. Whereas bulk lymph node cells from wild-type TCR
Tg mice expressed high levels of CD30 on T cells when stimulated with
peptide alone, CD28-deficient T cells bearing the same TCR transgene
failed to express CD30 (Fig. 3A, upper panel and
lower panel, respectively). Comparable levels of CD30 were
induced on wild-type T cells in cultures containing 10-fold less
peptide, suggesting that the failure to induce CD30 expression on
CD28-deficient T cells was not due to a suboptimal Ag dose. These data
indicated that under this set of culture conditions no other surface
receptor was able to substitute for CD28. CD28 has been shown to
mediate costimulatory effects both directly through induction of
intracellular signaling and indirectly through the augmentation of
cytokine production (29, 30, 31, 32). Therefore, we tested whether cytokines
could induce CD30 expression on CD28-deficient T cells. Because CD28 is
known to increase the expression of IL-2 (32, 33), the ability of rIL-2
to induce CD30 expression was tested in the absence of a CD28 signal.
Addition of rIL-2 to peptide stimulated bulk lymph node cells from
CD28-deficient TCR Tg mice did not augment CD30 expression (Fig. 3B, lower panel). In vitro IL-4 production
is also impaired in CD28-deficient mice (31). Therefore, we also tested
whether rIL-4 could function to induce CD30 expression in the absence
of CD28. Addition of rIL-4 was able to induce CD30 on CD28-deficient
TCR Tg lymph node cells stimulated with peptide (Fig. 3C,
lower panel). It also appeared that rIL-4 could
further enhance CD30 levels on wild-type TCR Tg cells over those levels
observed with peptide alone or peptide and rIL-2 (Fig. 3C,
upper panel).
|
To further test the roles of CD28 ligation and IL-4 in the
induction of CD30, wild-type TCR Tg lymph node cells were incubated
with peptide alone, peptide and CTLA4-Ig, or peptide and anti-IL-4.
As observed earlier, CD30 expression on wild-type T cells was
up-regulated when incubated with peptide alone (Fig. 4A). However when bulk
lymph node cells were incubated with peptide in the presence of either
CTLA4-Ig or anti-IL-4, induction of CD30 expression was
significantly suppressed (Fig. 4, B and C,
respectively). These data are indicative of a requirement for both CD28
and IL-4 signal transduction to up-regulate CD30 expression on T cells
activated by peptide in the presence of APCs. These data also suggest
that the ability of CD28 to induce CD30 expression is mediated, at
least in part, through augmentation of IL-4 expression.
|
If CD28 functions to up-regulate CD30 solely via indirect
effects on the IL-4 pathway, one prediction is that IL-4-deficient mice
would fail to express CD30 when stimulated with anti-CD3 and
anti-CD28. However, when bulk lymph node cells from IL-4-deficient
mice were stimulated with anti-CD3 and anti-CD28 for 5 days,
CD30 expression was induced in the majority of
Thy-1.2+ cells (Fig. 5B, upper
panel). This finding suggested that CD28 could exert
effects on CD30 expression independent of IL-4. The results in Figure 5B were mirrored when IL-4 was depleted from the
anti-CD3 and anti-CD28 treated wild-type bulk lymph node
cultures (Fig. 5C, lower panel). That is,
the addition of anti-IL-4 decreased but did not eliminate the
expression of CD30 on activated T cells provided with maximal
anti-CD28 costimulation. Although the expression of CD30 in the
presence of anti-IL-4 appeared bimodal, the populations that
displayed differential CD30 expression did not partition by cell
surface memory markers nor T cell subclass as defined by CD4, CD8,
Mel-14, and CD44 (data not shown). The lack of an effect of
anti-IL-4 in the IL-4-deficient mice assures the specificity of
this reagent (Fig. 5C, upper panel). This
dose of anti-IL-4 was sufficient to neutralize the effects of
10,000 U/ml rIL-4; therefore the result obtained with the wild-type
mice is most likely not due to a partial block of IL-4 produced in the
culture (data not shown). Therefore, it appears that the addition of
anti-IL-4 to wild-type cultures reduces CD30 expression to levels
comparable to that observed on IL-4-deficient T cells cultured with
anti-CD3 and anti-CD28 alone. Taken together, these data
suggest that CD28 induces CD30 expression through both IL-4-dependent
and IL-4-independent mechanisms.
|
One possible mechanism of IL-4-independent induction of CD30 could
be through an IL-13-mediated signal(s). IL-4 and IL-13 are cytokines
that display significant sequence similarity (34). In addition, they
have been reported to share common receptor subunits (35, 36) and can
induce many of the same biologic responses in B cells including the
up-regulation of both CD23 and MHC class II expression (37). Therefore,
we sought to determine whether IL-13 shared the ability of IL-4 to
activate CD30 expression in T cells. Figure 6 demonstrates that T cells treated with
anti-CD3 and rIL-4 expressed CD30. However, T cells stimulated with
anti-CD3 alone or with anti-CD3 and rIL-13 failed to express
CD30 (Fig. 6). IL-13 was originally defined as a cytokine that is
induced by CD28 (34). Therefore we also tested whether the depletion of
IL-13 in the context of anti-CD3 and anti-CD28 stimulation
would attenuate CD30 expression. Addition of anti-IL-13 had no
effect on the induction of CD30 expression by CD28. However, expression
of CD30 by a population of T cells was blocked when IL-4 was depleted
from anti-CD3 and anti-CD28 stimulated cultures (Figs. 5 and 6). These data suggest that although IL-4 and IL-13 functionally
overlap in many biologic systems, in the case of CD30 induction, the
two cytokines are distinct.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
and 6, and data not shown). In addition, the CD28 effects that
are independent of IL-4 are not due to the IL-4-related cytokine, IL-13
(Fig. 6). Although IL-13 can mimic many of the effects of IL-4, IL-13
failed to mimic the ability of IL-4 to promote CD30 expression on
activated T cells.
While our manuscript was in preparation, Nakamura et al. (38) reported
a study of cytokine regulation of CD30 expression. They concluded using
CD4+ TCR Tg mice that the presence of IL-4 was
essential for the induction of surface CD30 expression; however, the
significance of costimulation was not addressed in their study. In
addition, in contrast to our report, they found that in cultures
stimulated by the addition of peptide alone T cells failed to express
CD30. This could be attributed to at least three apparent differences:
genetic background of mice, use of purified CD4+ T cells
with irradiated APCs, and/or use of different TCR transgenes. In our
experiments utilizing TCR Tg mice we determined that blockade of the
CD28/B7 interaction(s) or depletion of IL-4 during peptide stimulation
of wild-type mice prevented CD30 expression. This finding may be due to
the reported requirement for CD28 costimulation for the acquisition of
IL-4 responsiveness by both Th1 and Th2 clones (39, 40). CD30
expression has been shown to be associated with Th2 clones (41, 42);
this observation is most likely explained by the use of IL-4 in the
induction and maintenance of Th2 clones, and the fact that Th2 clones
produce IL-4. Since we demonstrated that IL-4 in trans
augments CD30 expression on CD28-deficient T cells, T cells from
CD28-deficient mice may be able to induce CD30 expression and receive
subsequent costimulatory signals by CD30 as a result of IL-4 produced
by accessory cells in vivo. Nakamura et al. (38) also observed that Th0
cells which produce both IL-4 and IFN-
expressed CD30 and concluded
through additional studies that CD30 expression correlated with the
ability of T cells to respond to IL-4. We have observed that wild-type
lymph node cells stimulated with anti-CD3 and anti-CD28 for 5
days retain a Th0 phenotype and produce IFN- and IL-4 upon
restimulation (data not shown).
The fact that IL-4-deficient cells express CD30 in response to anti-CD3 and anti-CD28 stimulation precludes IL-4 as the sole regulator of CD30 expression in all instances of T cell activation. It remains possible that responsiveness to IL-4 is indicative of a late stage differentiation event that is independent of Th cell phenotype. This event could potentially be marked by the expression of CD30. Our findings are consistent with the previously reported role of CD28 in general T cell differentiation (29, 31) and also suggest that CD30 expression may correlate with the transition from a naive to a committed or differentiated cell.
We have also shown that CD30 can function as a costimulatory receptor in a T cell secondary proliferative response. Recently another member of the TNFR family, 4-1BB, was reported to be expressed at peak levels 2 to 3 days following T cell activation (43), and was determined to augment proliferation of T cells (43, 44). CD30 expression peaks later than 4-1BB, therefore, it will be of interest to analyze whether cross-talk between the different TNFR family members occurs or whether their functions are temporally distinct. Another possible functional distinction could be differential effects of each receptor on CD4+ vs CD8+ T cells. In our culture system, 95% of the cells proliferating in response to anti-CD3 and anti-CD30 crosslinking are CD4+ cells. In contrast, Shuford et al. (45) recently reported that 4-1BB predominantly costimulates CD8+ T cells.
Our lab and others have previously reported that CD30 signal
transduction induces NF-B activity (12, 13, 46, 47), which is
consistent with the positive effect of CD30 on proliferation. This
finding is also in accord with the published report concerning
CD30-deficient mice wherein negative selection of thymocytes is
impaired, as marked by hypercellularity of the thymus and impaired
deletion using the H-Y Tg model system (19). As signals which increase
the avidity of thymocyte interaction with the thymic
epithelium can augment negative selection (48, 49), it is likely that a
signal which is perceived as costimulatory during peripheral activation
such as CD30 could lead to deletion in the thymus. This exemplifies a
persistent question in the biology of immune cell function. How do the
same external stimuli result in divergent effects? For example,
anti-CD3 which provides a mitogenic signal in primary T cell
activation (4) can act as a death stimulus in immature T cells (50).
Part of the answer may result from synergistic interaction between
signaling pathways. This is seen in B cells that undergo apoptosis when
signaled via either surface Ig or CD40 alone (7, 8, 9, 10, 51, 52). But
simultaneous stimulation through both receptors potently triggers
survival and proliferation (7, 8, 9, 10). How these distinct outcomes are
regulated will presumably be answered when precise molecular signaling
pathways are elucidated and quantitated for each condition.
Nevertheless, the data presented in this report demonstrate the
potential of CD30, expression of which is dependent on early
costimulatory signals, to act as a positive regulator of activated T
cell function.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
2 Address correspondence and reprint requests to Dr. Craig B. Thompson, The University of Chicago, Gwen Knapp Center, 924 E. 57th Street, Room R413A, Chicago, IL 60637-5420.
3 Abbreviations used in this paper: TNFR, TNF receptor; TRAF, TNFR-associated factor; PE, phycoerythrin.
Received for publication August 21, 1997. Accepted for publication November 11, 1997.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
B by the CD30 receptor is mediated by TRAF1 and TRAF2. Mol. Cell. Biol. 17:1535.[Abstract]
B activation. Proc. Natl. Acad. Sci. USA 93:14053. production. J. Exp. Med. 179:299. and interleukin-4 receptor-
. Biochem. J. 319:865.
. J. Immunol. 158:2090.[Abstract]
B activation and binding specificity. Proc. Natl. Acad. Sci. USA 93:9699.This article has been cited by other articles:
|
|
 |
|
  S.-Y. Nam, Y.-H. Kim, J.-S. Do, Y.-H. Choi, H.-J. Seo, H.-K. Yi, P.-H. Hwang, C.-H. Song, H.-K. Lee, J.-S. Kim, et al. CD30 supports lung inflammation Int. Immunol., February 1, 2008; 20(2): 177 - 184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. C. Beier, T. Kallinich, and E. Hamelmann Master switches of T-cell activation and differentiation Eur. Respir. J., April 1, 2007; 29(4): 804 - 812. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Dai, I. W. Nasr, M. Reel, S. Deng, L. Diggs, C. P. Larsen, D. M. Rothstein, and F. G. Lakkis Impaired Recall of CD8 Memory T Cells in Immunologically Privileged Tissue J. Immunol., February 1, 2005; 174(3): 1165 - 1170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Florido, M. Borges, H. Yagita, and R. Appelberg Contribution of CD30/CD153 but not of CD27/CD70, CD134/OX40L, or CD137/4-1BBL to the optimal induction of protective immunity to Mycobacterium avium J. Leukoc. Biol., November 1, 2004; 76(5): 1039 - 1046. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. L. Stephens, R. S. McHugh, M. J. Whitters, D. A. Young, D. Luxenberg, B. M. Carreno, M. Collins, and E. M. Shevach Engagement of Glucocorticoid-Induced TNFR Family-Related Receptor on Effector T Cells by its Ligand Mediates Resistance to Suppression by CD4+CD25+ T Cells J. Immunol., October 15, 2004; 173(8): 5008 - 5020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. R. Blazar, R. B. Levy, T. W. Mak, A. Panoskaltsis-Mortari, H. Muta, M. Jones, M. Roskos, J. S. Serody, H. Yagita, E. R. Podack, et al. CD30/CD30 Ligand (CD153) Interaction Regulates CD4+ T Cell-Mediated Graft-versus-Host Disease J. Immunol., September 1, 2004; 173(5): 2933 - 2941. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. P. de Jong, S. T. Rietdijk, W. A. Faubion, A. C. Abadia-Molina, K. Clarke, E. Mizoguchi, J. Tian, T. Delaney, S. Manning, J.-C. Gutierrez-Ramos, et al. Blocking inducible co-stimulator in the absence of CD28 impairs Th1 and CD25+ regulatory T cells in murine colitis Int. Immunol., February 1, 2004; 16(2): 205 - 213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Toennies, J. M. Green, and R. H. Arch Expression of CD30 and Ox40 on T lymphocyte subsets is controlled by distinct regulatory mechanisms J. Leukoc. Biol., February 1, 2004; 75(2): 350 - 357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Harlin, E. Podack, M. Boothby, and M.-L. Alegre TCR-Independent CD30 Signaling Selectively Induces IL-13 Production Via a TNF Receptor-Associated Factor/p38 Mitogen-Activated Protein Kinase-Dependent Mechanism J. Immunol., September 1, 2002; 169(5): 2451 - 2459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. W. Chan, C. D. Hopke, S. M. Krams, and O. M. Martinez CD30 Expression Identifies the Predominant Proliferating T Lymphocyte Population in Human Alloimmune Responses J. Immunol., August 15, 2002; 169(4): 1784 - 1791. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Panus, C. A. Smith, C. A. Ray, T. D. Smith, D. D. Patel, and D. J. Pickup Cowpox virus encodes a fifth member of the tumor necrosis factor receptor family: A soluble, secreted CD30 homologue PNAS, June 11, 2002; 99(12): 8348 - 8353. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kemp, J. A. L. Kurtzhals, B. D. Akanmori, V. Adabayeri, B. Q. Goka, C. Behr, and L. Hviid Increased Levels of Soluble CD30 in Plasma of Patients with Plasmodium falciparum Malaria Clin. Vaccine Immunol., May 1, 2002; 9(3): 720 - 722. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Yamada, A. D. Salama, and M. H. Sayegh The Role of Novel T Cell Costimulatory Pathways in Autoimmunity and Transplantation J. Am. Soc. Nephrol., February 1, 2002; 13(2): 559 - 575. [Full Text] [PDF]
|
|
|
|
 |
|
 F. Vinante, A. Rigo, M. T. Scupoli, and G. Pizzolo CD30 triggering by agonistic antibodies regulates CXCR4 expression and CXCL12 chemotactic activity in the cell line L540 Blood, January 1, 2002; 99(1): 52 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. T. Seah and G. A. W. Rook IL-4 Influences Apoptosis of Mycobacterium-Reactive Lymphocytes in the Presence of TNF-{alpha} J. Immunol., August 1, 2001; 167(3): 1230 - 1237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Mir, B. W. M. Richter, and C. S. Duckett Differential effects of CD30 activation in anaplastic large cell lymphoma and Hodgkin disease cells Blood, December 15, 2000; 96(13): 4307 - 4312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Muta, L. H. Boise, L. Fang, and E. R. Podack CD30 Signals Integrate Expression of Cytotoxic Effector Molecules, Lymphocyte Trafficking Signals, and Signals for Proliferation and Apoptosis J. Immunol., November 1, 2000; 165(9): 5105 - 5111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Cerutti, A. Schaffer, R. G. Goodwin, S. Shah, H. Zan, S. Ely, and P. Casali Engagement of CD153 (CD30 Ligand) by CD30+ T Cells Inhibits Class Switch DNA Recombination and Antibody Production in Human IgD+ IgM+ B Cells J. Immunol., July 15, 2000; 165(2): 786 - 794. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Annunziato, P. Romagnani, L. Cosmi, C. Beltrame, B. H. Steiner, E. Lazzeri, C. J. Raport, G. Galli, R. Manetti, C. Mavilia, et al. Macrophage-Derived Chemokine and EBI1-Ligand Chemokine Attract Human Thymocytes in Different Stage of Development and Are Produced by Distinct Subsets of Medullary Epithelial Cells: Possible Implications for Negative Selection J. Immunol., July 1, 2000; 165(1): 238 - 246. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Kadin Regulation of CD30 Antigen Expression and Its Potential Significance for Human Disease Am. J. Pathol., May 1, 2000; 156(5): 1479 - 1484. [Full Text] [PDF]
|
|
|
|
|
|
R. Chiarle, A. Podda, G. Prolla, E. R. Podack, G. J. Thorbecke, and G. Inghirami CD30 Overexpression Enhances Negative Selection in the Thymus and Mediates Programmed Cell Death Via a Bcl-2-Sensitive Pathway J. Immunol., July 1, 1999; 163(1): 194 - 205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Jones, C. D.M. Fletcher, K. Pulford, A. Shahsafaei, and D. M. Dorfman The T-Cell Activation Markers CD30 and OX40/CD134 Are Expressed in Nonoverlapping Subsets of Peripheral T-Cell Lymphoma Blood, May 15, 1999; 93(10): 3487 - 3493. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Jeannin, N. Herbault, Y. Delneste, G. Magistrelli, S. Lecoanet-Henchoz, G. Caron, J.-P. Aubry, and J.-Y. Bonnefoy Human Effector Memory T Cells Express CD86: A Functional Role in Naive T Cell Priming J. Immunol., February 15, 1999; 162(4): 2044 - 2048. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Weinberg, K. W. Wegmann3, C. Funatake, and R. H. Whitham Blocking OX-40/OX-40 Ligand Interaction In Vitro and In Vivo Leads to Decreased T Cell Function and Amelioration of Experimental Allergic Encephalomyelitis J. Immunol., February 1, 1999; 162(3): 1818 - 1826. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
