title: 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-β 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.
authors.affiliation: Section of Nephrology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Guilin
authors.initials: G
authors.lastname: Qiao
authors.forename: Lifen
authors.initials: L
authors.lastname: Yang
authors.forename: Zhenping
authors.initials: Z
authors.lastname: Li
authors.forename: Haiyan
authors.initials: H
authors.lastname: Ying
authors.forename: Yassir
authors.initials: Y
authors.lastname: Hassen
authors.forename: Fei
authors.initials: F
authors.lastname: Yin
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003092:Colitis / Q000209:etiology / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D061026:Programmed Cell Death 1 Receptor / Q000172:deficiency / Q000235:genetics / Q000276:immunology*
chemical_list: D018398:Homeodomain Proteins; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; C064658:RAG-1 protein