过度激活的免疫反应尤其是由CD4+T淋巴细胞介导的免疫反应（包括自身免疫反应）是病毒性心肌炎（VMC）心肌细胞损伤的重要原因。我们前期的研究显示，Th17细胞及其效应分子IL-17参与了VMC的发病，但IL-17抗体并不能完全阻断VMC的炎症过程。Tfh细胞是一个新的CD4+T细胞亚群,其分化、分布或效应分子异常,均可造成免疫系统紊乱,引发自身免疫疾病，但Tfh细胞在VMC中的作用尚未见报道。本项目应用CVB3建立VMC小鼠模型，探讨Tfh细胞在小鼠VMC不同时期的变化规律及其与抗腺嘌呤核苷酸转位子(ANT)抗体的相关性；通过IL-21抗体和IL-21-/-小鼠，观察干预后VMC小鼠心肌病理改变、Tfh细胞、B细胞增殖及抗ANT抗体的影响；探讨CXCL13介导Tfh细胞辅助B细胞产生抗ANT抗体的机制。本项目从Tfh细胞这个新角度，为探索VMC的发病机制、寻求VMC治疗靶点提供新线索。

Excessive activated immune response, especially mediated by CD4+ T lymphocytes (including autoimmune reaction), is the important reason of myocardial damage in viral myocarditis (VMC). Our initial research shows that, Th17 cells and its effect cytokine IL-17 involved in the pathogenesis of VMC, but IL-17 antibody could not compeletly block the inflammation of VMC. Tfh cells is a new group of CD4+T cells, whose differentiation, distribution or effect molecular abnormalities would cause the disorder of immune system and trigger autoimmune disease. Until now, the role of Tfh cells in VMC has not been reported. This project is to establish the change of Tfh cells during different periods of VMC (murine model, induced by CVB3 peritoneal injection), to explore the relationship between Tfh cells and adenine nucleotide translocator (ANT) antibody. Using IL-21 antibody and IL-21 -/- mice, we aim to observe the pathological changes of myocardiums, the B cell proliferation and the influence of the ANT antibodies. What more, this study aim to elucidate the mechanism by which Tfh cells assist the B cells to produce ANT antibody. This project will further provide new clues for clarifing the pathogenesis of VMC and therapeutic targets of VMC from a new perspective of Tfh cells.