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Program death-1 regulates peripheral T cell tolerance via an anergy-independent mechanism.

ABSTRACT: 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-? 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.

SUBMITTER: Qiao G

PROVIDER: S-EPMC3327760 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Program death-1 regulates peripheral T cell tolerance via an anergy-independent mechanism.

Qiao Guilin G Yang Lifen L Li Zhenping Z Ying Haiyan H Hassen Yassir Y Yin Fei F Zhang Jian J

Clinical immunology (Orlando, Fla.) 20120309 2

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-β in vitro. In support of this finding, PD-1 deficie ...[more]

PMID: 22459706

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