Critical Role of the Programmed Death-1 (PD-1) Pathway in Regulation of Experimental Autoimmune Encephalomyelitis

• DOI: 10.1084/jem.20022119
• Publication Date: 2003-07-07T21:12:21Z
• Authors: Alan D. Salama; Tanuja Chitnis; Jaime Imitola; Mohammed Javeed I...; Hisaya Akiba; Fumihiko Tushima; Miyuki Azuma; Hideo Yagita; Mohamed H. Sayegh; Samia J. Khoury
• Keywords: Myelin oligodendrocyte glycoprotein; Encephalomyelitis; Central tolerance; Peripheral tolerance

Experimental autoimmune encephalomyelitis (EAE) is mediated by autoantigen-specific T cells dependent on critical costimulatory signals for their full activation and regulation. We report that the programmed death-1 (PD-1) pathway plays a role in regulating peripheral tolerance murine EAE appears to be major contributor resistance of disease induction CD28-deficient mice. After immunization with myelin oligodendrocyte glycoprotein (MOG) there was progressive increase expression PD-1 its ligand PD-L1 but not PD-L2 within central nervous system (CNS) mice EAE, peaking after 3 wk. In both wild-type (WT) mice, blockade resulted accelerated more severe increased CNS lymphocyte infiltration. Worsening associated heightened response MOG, manifested frequency interferon γ–producing cells, delayed-type hypersensitivity responses, higher serum levels anti-MOG antibody. vivo antigen-specific cell expansion, activation, cytokine production. Interestingly, WT animals also augmentation. Our data are first demonstration EAE.