共刺激分子B7-H1转染角朊细胞对T细胞增殖、细胞因子分泌和表面标记的作用  

Effects of Kerationcytes Transfected with Costimulatory Molecule B7-H1 on the Proliferation,Secretion of Cytokines and Surface Markers of T Cells

作　　者：陶箭[1] 周芸[1] 王胜旺[1] 王保龙[1] 张汉明[1] 程琳琳[1] 张冬青[1] 周光炎[1] 

机构地区：[1]上海第二医科大学上海市免疫学研究所,上海200025

出　　处：《上海免疫学杂志》2003年第6期365-369,共5页Shanghai Journal of Immunology

基　　金：国家自然科学基金资助项目 (No 3 0 170 864 )

摘　　要：分析B7 H1共刺激分子阳性细胞激活的T细胞亚群表面标志和细胞因子分泌格局的变化 ,初步鉴定所诱导具有调节功能的人体T细胞亚群生物学特性。用抗CD3、CD2 8抗体分别作为第一和第二信号的来源 ,建立了T细胞体外增殖体系 ,引入B7 H1阳性A4 31细胞。结果表明B7 H1阳性A4 31细胞提供第二信号并加入抗CD3分子时 ,引起纯化的T细胞中等程度增殖 ,IL 10和TGF β升高 ,CD4 5RBlowT细胞亚群比例增加。而在阳性对照组 (同时加抗CD3和抗CD2 8抗体 )可见T细胞高度增殖 ,此时再加入B7 H1阳性A4 31细胞 ,增殖反应受到抑制 ,加入B7 H1封闭型单抗 ,抑制缓解。认为B7 H1阳性A4 31细胞具有双向效应 :当CD2 8不参与共刺激时 ,由B7 H1发挥共刺激作用 ,协同抗CD3抗体引起T细胞增殖 ;一旦T细胞从抗CD3和抗CD2 8抗体获得第一和第二信号出现高度增殖时 ,B7 H1阳性A4 31细胞发挥抑制作用。B7 H1阳性A4 31细胞提供第二信号的T细胞增殖 ,含有呈现典型Tr1细胞表型。针对增殖性T细胞应答 (如移植排斥 ) ,表达B7 H1的非专职性抗原递呈细胞KC ,可选择性诱导人体调节性T细胞 (Tr1)的分化 ,发挥负向调节作用。To analyze the cytokine profile and the expression patterns of surface markers on T cell subsets activated by the B7-H1 positive keratinocytes,the biological characteristcs could be preliminarily defined for T cell subset capable of down-regulating the allo-reaction. By using anti-CD3 and/or anti-CD28 monoclonal antibodies for offering the first and second signals,an in vitro proliferation system was set up,and the B7-H1 positive A431 cells was introduced herein. The results revealed that the costimulatory signal delivered by B7-H1 positive A431 cells led to a moderate proliferation of T cells,when stimulated with anti-CD3 and anti-CD28 antibodies added together. When the B7-H1 positive A431 cells were superimposed on the positive control,the proliferation of T cells was depressed to a much lower level. Anti-B7-H1 monoclonal antibody could diminish the suppression. At the same time,there were an enhanced secretions of IL-10 and TGF-β,as well as the appearance of CD45RB low marker. The results implicate a reversible effect of B7-H1 molecule,without involving the CD28 with its ligand,B7-H1 molecule is able to behave as a costimulator to initiate proliferation of lymphocytes in cooperation with anti-CD3 monoclonal antibody. Once T cells proliferate intensively following the stimulation by anti-CD3 and anti-CD28 antibodies,the B7-H1 molecule expressed on the A431 cells exerts its inhibitory effect. Phenotypically,they have the typical phenotype of Tr1 cell,a regulatory T cell suset. It is thus reasonable to postulate that the differentiation on the Tr1 cells can be induced by keratinocytes transfected with B7-H1 molecule to express its down-regulatory effect.

关 键 词：B7-H1 共刺激分子 角朊细胞 T细胞增殖 细胞因子 表面标记 调节性T细胞 

分 类 号：R392.12[医药卫生—免疫学]