调节性B细胞在结核性胸膜炎发病机制中的作用

In order to investigate the immune regulatory roles of B lymphocytes in tuberculous, this study will use tuebrculous pleural effusion (TPE) as a research model to extend our previous works and 1) will elucidate the distribution of subgroupof B cells and phenotypic characteristics of Breg cells in TPE, and their association with various clinical parameters; 2) will identify the presence or absence of various cytokines requiring for generation of Breg cells,and the cell origins of these cytokines, as well as the mechanisms by which synthesis and release of cytokines are affected; 3) will explore the optimal conditions for cytokine production by Breg cells, and the involved signal pathways;4) will elucidate the effects and mechanisms of Breg cells on generation and differentiation of Th1,Th9,Th17,Th22 and Treg cells in vitro; 5) will investigate the effects of Breg on antigen presenting and fibrosis of pleural mesothelium; 6) will elucidate the mechanism by which Breg cells are recruited into the pleural space and Breg cells on prognosis of patients with TPE. This study will elucidate the roles of Breg cells in the pathogenesis of TPE, identify the reciprocal functions of humoral immunity and cellular immunity to shape the immune responses to Mtb.infection,and will lead to the design of novel strategies, including the development of effctive vaccines, to better control TB.

为了探讨调节性B淋巴细胞（Breg）在结核杆菌感染中的免疫调节作用，本项目将以结核性胸腔积液（TPE）为模型，在以前工作的基础上揭示TPE中Breg细胞的表型和功能特征及其与临床指标之间的关系；确定TPE中是否存在调节Breg细胞发生及免疫学功能的各种细胞因子；在体外实验中阐明Breg细胞分泌细胞因子所需要的最适宜条件，并阐明Breg细胞与CD4+ T细胞亚群如Th1、Th9、Th17、Th22、Treg细胞等之间的相互作用及其作用机制；以及Breg对胸膜间皮细胞呈递抗原、上皮间质转化的影响及其机制；揭示Breg细胞浸润到胸膜腔的机制及其与TPE转归的影响。本项目的完成将加深对TPE中Breg细胞免疫学特征的认识，深入研究体液免疫和细胞免疫在结核感染中的相互作用及调节机制，为临床研发安全有效的疫苗、探求新的结核治疗策略奠定理论基础。

在本面上项目（81470274）研究经费的资助下，取得了如下研究成果：(1)白细胞介素-27对于结核性胸膜炎有较高的诊断价值。在结核病高度流行的地区，胸液中的白介素27可以用于诊断TPE，而在所有的流行地区，阴性结果能够可靠地排除TPE。(2) 首次发现结核性胸腔积液中的IL-26水平显著高于外周血中的浓度，胸水中的Th1细胞和Th17细胞是IL-26的主要来源，IL-26促进CD4+T细胞分泌IL-22进而参与TPE的发病过程。(3) 结合文献总结了表达在CD8+调节性T细胞和CD8+效应性T细胞上的TNFR2的生物学功能，强调了TNF如何通过TNFR2协调并最终引起有效的CD8+T细胞介导的免疫反应。(4) 探讨B细胞亚群在TPE和外周血中的分布特点。结果表明胸水中非转化记忆细胞（IgD+CD27+）、浆细胞IgD-CD27+CD38++ ）及调节性B细胞（CD24+CD27+）的比例显著高于外周血。