共刺激分子pd-pd-l2在类风湿关节炎组织内的-第三军医大学学报.docVIP

B7-H4在类风湿关节炎组织内的表达及分布研究 郭国宁① 　尚永军②　朱国宴③　文 　亮④　向强① 　(第三军医大学附属西南医院急诊科 ,重庆 400038) ①本文受国家自然科学基金60971117)资助 ②内蒙古赤峰学院第一附属医院骨科,赤峰 024000 ③重庆江陵医院妇产科,重庆 400038 ④通讯作者 作者简介: 郭国宁(1974年- )，男，博士，主治医师，主要从事免疫调节的基础及临床研究，E-mail：gotoguoguo@126.com 通讯作者：文亮 摘 要 目的：探讨共刺激分子B7-H4在牛二型胶原（CII）Expression and distribution of the costimulatory molecule B7-H4 in tissues from rheumatoid arthritis ABSTRACT Objective Detecting B7-H4 protein expression in tissues from bovine collagen II （CII）- induced mouse rheumatoid arthritis (CIA) and synovial tissues of RA patients. Methods The expression and distribution of B7-H4 antigen was analyzed by immunohistochemistry. Moreover, fluorescence double-staining was further used to characterize B7-H4 expression. Results Immunohistochemical analysis revealed that B7-H4 positive cells were found in thymus, spleen, lymph nodes and bone marrow, and fluorescence double-staining further demonstrated that B7-H4 positive cells were CD31+ endothelial cells. However, the expression and distribution of B7-H4 was not changed significantly between normal and CIA mice. Interestingly, high level of B7-H4 positive cells was found both in synovial tissues of CIA mice and RA patients. Conclusion Expression of B7-H4 was observed on the surface of antigen presentation cells such as endothelial cells within immune organs and synovial tissues of CIA mice and RA patients, indicated this signal might be involved in regulating local T cell activation and finally participated in the pathogenesis of RA. Keywords: B7-H4; rheumatoid arthritis; synovial tissues; immune organs; immunohistochemistry 类风湿关节炎(Rheumatoid Arthritis，RA)是以对称性多关节滑膜炎为主要临床症状的自身免疫性疾病，呈慢性、进行性、迁延性。多数病人有永久性骨破坏，并可出现关节外损害，如脏器和神经系统受累，若无恰当治疗，则最终形成终生残疾甚至危及生命(1)。γ和TNF-α等数种炎症因子，从而促进滑膜细胞异常增殖和血管翳形成，最终导致关节软骨和软骨下骨的破坏(2,3)。 对T细胞活化机制的研究表明，T细胞的有效活化和效应发挥需要共刺激信号，缺乏共刺激信号的抗原刺激易引起免疫耐受(Tolerance)或无反应性(Anergy) (4)。已知的几种共刺激分子(CD28，CTLA-4，ICOS，PD-1及BTLA等)在多种疾病包括类风湿关节炎中有主导作用（4）。如：使用CTLA-4-Ig融合蛋白对RA患者进行治疗的研究发现，CTLA-4-Ig治疗6个月后，患者关节