期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 34, 期 11, 页码 2996-3005出版社
WILEY
DOI: 10.1002/eji.200425143
关键词
T lymphocytes; tolerance/suppression/anergy; costimulation; cytokines
类别
资金
- NIAID NIH HHS [F32 AI10360, AI466430] Funding Source: Medline
Both CTLA-4 and TGF-beta have been implicated in suppression by CD4(+)CD25(+) regulatory T cells (Treg). In this study, the relationship between CTLA-4 and TGF-beta in Treg function was examined. Blocking CTLA-4 on wild-type Treg abrogated their suppressive activity in vitro, whereas neutralizing TGF-beta had no effect, supporting a TGF-beta-independent role for CTLA-4 in Treg-mediated suppression in vitro. In CTLA-4-deficient mice, Treg development and homeostasis was normal. Moreover, Treg from CTLA-4-cleficient mice exhibited uncompromised suppressive activity in vitro. These CTLA-4-cleficient Treg expressed increased levels of the suppressive cytokines IL-10 and TGF-P, and in vitro suppression mediated by CTLA4(-/-)Treg was markedly reduced by neutralizing TGF-beta, suggesting that CTLA-4-deficientTreg develop a compensatory suppressive mechanism through CTLA-4-independent production of TGF-beta. Together, these data suggest that CTLA-4 regulates Treg function by two distinct mechanisms, one during functional development of Treg and the other during the effector phase, when the CTLA-4 signaling pathway is required for suppression. These results help explain contradictions in the literature and support the existence of functionally distinct Treg.
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