Journal
CLINICAL IMMUNOLOGY
Volume 143, Issue 2, Pages 128-133Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2012.02.006
Keywords
Costimulation; Tolerance/suppression/anergy; T cell
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Funding
- National Institutes of Health (NIH) [R01 AI090901]
- American Heart Association [09GRNT2010084]
- China Scholarship Council of the Ministry of Education of PR China [[2007] 3020]
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Program death-1 (PD-1) has been documented to negatively regulate immune responses. However, the cellular and molecular mechanisms for PD-1-mediated immune suppression have not been fully elucidated. In this study, we show that loss of PD-1 does not lead to defective induction of CD4(+) T cell anergy in vitro and in vivo. Rather, the absence of PD-1 inhibits the development of inducible CD4(+)Foxp3(+) regulatory T cells (iTregs) induced by TGF-beta in vitro. In support of this finding, PD-1 deficiency impairs the generation of iTregs in vivo and leads to development of severe T cell-transfer-induced colitis. Mechanistically, defective iTreg generation in the absence of PD-1 was attributed to the heightened phosphorylation of Akt. Therefore, we first demonstrate that PD-1 controls peripheral T cell tolerance via an anergy-independent but iTreg-dependent mechanism. (C) 2012 Elsevier Inc. All rights reserved.
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