Graves病（GD）缺乏有效治疗方式且发病机制不明。前期研究发现，CTLA-4Ig可以在GD小鼠中诱导免疫耐受，同时Tfh细胞相关因子表达下降，提示CTLA-4Ig重建GD免疫耐受中Tfh细胞受到抑制。同时文献表明：CTLA-4是抑制Tfh细胞功能的关键因子，Tfh细胞是辅助B细胞产生自身抗体的最主要细胞，而B细胞产生抗体TRAb是GD发病的核心因素。据此，我们提出假说：CTLA-4Ig通过抑制Tfh细胞功能，降低B细胞分化及TRAb产生来重建GD免疫耐受。本研究中，我们将利用GD病人Tfh与B细胞共培养系统，在体外考察CTLA-4对Tfh的调控作用。同时利用BCL-6基因敲除鼠构建GD模型，体内考察Tfh细胞在CTLA-4Ig重建GD免疫耐受中的作用。本研究的开展将有助于理解CTLA-4Ig重建GD免疫耐受的机制以及Tfh细胞在GD发生中的作用，进而为GD的免疫治疗提供理论基础和实验证据。.

Graves' disease (GD) lacks of effective treatment and its pathogenesis is not clear. Our preliminary study has confirmed that cytotoxic T-lymphocyte Antigen 4Ig (CTLA-4Ig) can restore the immune tolerance and lower the expression of T follicular helper (Tfh) in the GD mouse model. It has been found in the literature review that CTLA-4 is the key factor regulating the function of Tfh cells, which are the main ones helping B cells produce antibodies, and the thyrothrophin receptor antibody (TRAb) produced by B cells is the core factor resulting in the onset and relapse of GD. Therefore, we have proposed the hypothesis that CTLA-4Ig may restore the immune tolerance in GD patients through down-regulating the function of Tfh cells, B cell differentiation and TRAb production. In this study, we are going to explore the regulation of CTLA-4 on Tfh cells in vitro using a co-culture system of Tfh and B cells. Simultaneously, the GD mouse model with the BCL-6 gene knockout was used to explore the role Tfh cells play in CTLA-4Ig’s restoring the immune tolerance in vivo. This study will contribute to understanding the mechanism of CTLA-4Ig’s restoring the immune tolerance and the role Tfh cells play in the occurrence of GD, which will in turn provide a theoretical basis and experimental evidence for the latter’s immunological therapy.