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The PD-1/PD-L pathway is up-regulated during IL-12-induced suppression of EAE mediated by IFN-gamma

2007; Elsevier BV; Volume: 185; Issue: 1-2 Linguagem: Inglês

10.1016/j.jneuroim.2007.01.012

1872-8421

Xian Cheng, Zhongchao Zhao, E. Ventura, Bruno Gran, Kenneth S. Shindler, Abdolmohamad Rostami,

Immunotherapy and Immune Responses

Abstract Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), is mediated by autoantigen-specific T-helper1 (Th1) cells. IL-12, an inducer of Th1 cell development, exerts immunomodulatory effects in EAE. Programmed death-1 (PD-1) and PD-1 ligand (PD-L), new members of the B7 superfamily of costimulatory molecules, play a critical role in regulating EAE. Whether the interaction of IL-12 and the PD-1/PD-L pathway regulates EAE is unclear. We have previously shown that IL-12 suppresses EAE induced by MOG35–55 in C57BL/6 mice, but not in IFN-γ-deficient mice, suggesting that IFN-γ is required for the inhibitory effects of IL-12 on EAE. In the current study, PD-L1 expression is up-regulated following IL-12 treatment in wild-type mice, but not in IFN-(-deficient EAE mice. Similarly, IL-12 induces IFN-γ and PD-L1 expression in cultured MOG-specific T cells from wild-type mice but not from IFN-γ-deficient mice. Furthermore, PD-L1 expression increased specifically in CD11b+ antigen presenting cells (APCs) after IL-12 administration. These data suggest that one mechanism of IL-12 suppression of EAE is mediated by PD-1/PD-L signaling downstream of IFN-γ induction in CD11b+ APCs. The regulation of PD-1/PD-L1 may have potential therapeutic effects for EAE and MS.