CD4+TEM细胞介导小鼠病毒性心肌炎急性期向慢性期演变的研究

病毒性心肌炎(VMC)急性期后可演变为慢性心肌炎甚至扩张型心肌病（DCM），其演变机制主要与病毒感染后CD4+T细胞介导的自身免疫反应有关，但确切的免疫致病机制尚未完全阐明。有研究证实CD4+效应型记忆T细胞（TEM）参与慢性炎症和自身免疫疾病的发病过程，并且我们前期研究发现VMC小鼠和DCM患者体内CD4+效应型记忆样T细胞明显增多，因此我们推测CD4+TEM细胞有可能是介导VMC急性期向慢性期演变的重要因素。故本研究用心脏传代的柯萨奇病毒B3感染Balb/c小鼠建立VMC模型，观察VMC发病不同时期CD4+TEM细胞及其分泌IL-17A、IFN-γ等细胞因子的变化，分析过继CD4+TEM细胞对VMC急性期向慢性期演变的影响，并且用IL-17A基因敲除鼠和细胞体外共培养实验来探讨CD4+TEM细胞介导VMC急性期向慢性期演变的分子机制，旨在为人VMC演变为DCM的防治提供新靶点。

Viral myocarditis (VMC) can evolve into chronic myocarditis or even dilated cardiomyopathy(DCM) following the acute phase, and the evolution mechanism is mainly associated with the autoimmune response mediated by CD4+T cells following viral infection, but the exact immunopathogenic mechanism has not been fully elucidated. Lots of studies have confirmed that CD4+ effector memory T (TEM) cells are involved in the pathogenesis of chronic inflammation and autoimmune diseases, more over, our previous study found that CD4+ effector memory-like T cells increased significantly in mice with VMC and patients with DCM, thus we speculated that CD4+TEM cells may mediate the evolution of VMC from acute phase to chronic phase. In this study, Balb/c mice will be infected with heart-passaged CVB3 to establish VMC models, to observe the changes of CD4+TEM cells and their secretion of IL-17A, IFN-γ and other cytokines in different phases of VMC, to investigated the effects of CD4+TEM cells on the evolution of VMC from acute phase to chronic phase in mice by adoptive transfer experiments, and to explore the molecular mechanism of CD4+TEM cells mediating the evolution of VMC from acute phase to chronic phase using IL-17A knockout mice and by experiments in vitro. The aim of this study is to provide a new target for the prevention and treatment of human VMC evolving into DCM.