滤泡辅助性T细胞及其在免疫疾病中的应用

Follicular helper T cells and their application in immune diseases

滤泡辅助性T(follicular helper T,Tfh)细胞是近年新发现的受B细胞淋巴瘤6蛋白(Bcl-6)控制的一类独立CD4+T淋巴细胞亚群,以高表达趋化因子受体5(C-X-chemokine receptor type 5,CXCR5)、诱导性共刺激分子(inducible co-stimulator,ICOS)、程序性细胞死亡蛋白-1(programmed cell death protein 1,PD-1)及白细胞介素(IL)-21为特征。Tfh的功能是辅助B淋巴细胞在生发中心淋巴滤泡内活化、增殖、分化成为浆细胞,产生高亲和力免疫球蛋白,促进Ig亚群类别转换及记忆B细胞形成。既往研究证明,Tfh功能异常与免疫缺陷病、过敏、肿瘤、器官移植排斥反应及心脏病等密切相关。近年来研究发现Tfh在自身免疫疾病的发病机制中扮演了重要角色。本文总结了Tfh的来源、分化、转录调控,并对Tfh与系统性红斑狼疮、类风湿关节炎、原发性干燥综合征及1型糖尿病等自身免疫疾病的关系进行综述。

Follicular helper T(Tfh)cells are a type of newly discovered independent subgroup of CD4+T lymphocytes under the control of B cell lymphoma 6 protein(Bcl-6),which are characterized by high expression of C-X-chemokine receptor type 5(CXCR5),inducible co-stimulator(ICOS),programmed cell death protein(PD-1)and interleukin(IL)-21.The function of Tfh is to assist B lymphocytes to activate,proliferate and differentiate into plasma cells in the germinal center lymphatic follicles,so as to produce high-affinity immunoglobulin,and promote the classification conversion of Ig subgroups and the formation of memory B cells.Previous studies have shown that Tfh dysfunction is closely related to immunodeficiency disease,allergy,tumor,organ transplant rejection and heart disease.In recent years,it has been confirmed that Tfh also plays an important role in the pathogenesis of autoimmune diseases.This article reviews the origin,differentiation,transcriptional regulation of Tfh and its relationship with autoimmune diseases such as systemic lupus erythematosus,rheumatoid arthritis,primary Sj gren′s syndrome and type 1 diabetes.