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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。
The changes of T cell subsets surface markers and cytokine secretion patterns of B7-H1 co-stimulatory molecules positive cells were analyzed to identify the biological characteristics of human T cell subsets induced by regulatory factors. Using anti-CD3 and CD2 8 antibodies as the source of the first and second signals respectively, a T cell in vitro proliferation system was established and B7 H1 positive A431 cells were introduced. The results showed that B7H1-positive A431 cells, when provided with a second signal and addition of anti-CD3 molecules, caused a moderate increase in purified T cells with elevated levels of IL10 and TGFβ and an increased proportion of CD4 5RBlowT cell subsets. In the positive control group (plus anti-CD3 and anti-CD2 8 antibodies), T cells were highly proliferated. At this time, B7-H1-positive A431 cells were added and the proliferative responses were inhibited. B7 H1-blocking mAb was added to inhibit the remission. It is believed that B7H1-positive A431 cells have a bidirectional effect: co-stimulation by B7H1 when CD28 is not involved in costimulation and synergism with anti-CD3 antibody cause T cell proliferation; once T cells are obtained from anti-CD3 and anti-CD28 antibodies B7Hl -positive A431 cells exerted an inhibitory effect on the proliferation of one and the second signal. B7Hl -positive A431 cells provided T-cell proliferation of the second signal, containing the typical Trl cell phenotype. In response to proliferative T cell responses (such as transplant rejection), KC expressing non-specific antigen-presenting cells of B7-H1 selectively induces the differentiation of human regulatory T cells (Tr1), playing a negative regulatory role.