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It is widely acknowledged that interleukin 17-producing T helper (Th17) cells are critically participant in the pathogenesis of multiple sclerosis. In the current study, we identified that the expression of CD4 + T cells specific co-inhibitory molecule B7-homologue 1(B7-H1) in spleenocytes and mononuclear cells isolated from brains and spinal cord were positive correlated with Th1 and Th17 cells generation and disease severity in experimental autoimmune encephalomyelitis (EAE). Furthermore, B7-H1 transgenic mice developed milder EAE symptoms and fewer Th17 cells than B7-H1 wild type mice. We also found the proliferation of naïve CD4 + CD62 + T cells isolated from B7-H1 transgenic mice was inhibited. And naïve T cells isolated from B7-H1 transgenic mice produced fewer Th17 cells than WT mice in Th17-polarizing conditions, but the Th1, Th2, and inducible Treg differentiation were the similar in naïve T cells isolated from B7-H1 transgenic mice and WT mice. In conclusion, our study show CD4 + T cells specific B7-H1 is a slective inhibitor in proliferation of naïve T cells, Th17 differentiation and pathogenesis of multiple sclerosis., Competing Interests: CONFLICTS OF INTERETS None.