CD4+T cell specific B7-H1 selectively inhibits proliferation of naïve T cells and Th17 differentiation in experimental autoimmune encephalomyelitis.

Sheng-Jia Shi,Jie-Heng Wu,Wei-Jun Qin,Guo-Xu Zheng,Zhang-Yan Guo,Dong-Hui Han,Mei-Ling Ding,Wen-Jin Xi,Wei-Hong Wen,Li-Juan Wang,An-Gang Yang

doi:10.18632/oncotarget.21357

Abstract

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.

Highlights

Multiple sclerosis (MS) is a organ-specific autoimmune disease, which characterized by chronic inflammatory demylination of certral nervous system (CNS) [1]
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 The number of interleukin 17-producingT helper (Th17) cells generation and disease severity in experimental autoimmune encephalomyelitis (EAE)
As the EAE clinical score increasing from day 0 to day 19 after immunization of encephalitogenic peptide of myelin oligodendrocyte glycoprotein consisting of amino acids 35-55 (MOG (35-55)), CD4+IFN-γ+ (Figure 1A and Supplementary Figure 1A) and CD4+IL-17A+ (Figure 1B and Supplementary Figure 1A) cells in splenocytes and mononuclear cells infiltrated in central nervous system (CNS) were increasing

Summary

Introduction

Multiple sclerosis (MS) is a organ-specific autoimmune disease, which characterized by chronic inflammatory demylination of certral nervous system (CNS) [1]. Our results provide evidence that there is a significant positive correlations among CD4+T cells specific B7-H1 and Th17 production and EAE development. We found CD4+T cells specific B7-H1 could selectively inhibit naïve T cell proliferation and Th17 differentiation during EAE development.

Results

Conclusion