【摘要】 HVEM既可作为受体与LIGHT作用传递正性共刺激信号,又能作为配体作用于BTLA介导负性共抑制信号。为深入探讨HVEM对T细胞复杂而又独特的调控作用,本文研究了HVEM在免疫细胞上的表达特性,初步探讨了T细胞表达的HVEM分子所介导的生物学作用。采用LPS刺激人新鲜PBMC,以及PHA或PMA/IM刺激活化T细胞;间接免疫荧光标记和流式细胞术检测HVEM表达;MTT法分析T细胞增殖作用。结果显示,HVEM在不同条件刺激活化的T细胞表面均呈现先上调后下调表达;T细胞增殖试验表明,基因转染细胞L929/LIGHT能够明显促进T细胞的增殖及IL-2和IFN-γ的分泌,而以抗人BTLA单抗在一定程度上模拟HVEM所介导的BTLA/HVEM信号能够明显抑制T细胞增殖作用及细胞因子IL-2、IFN-γ和IL-10的产生。更多还原

【Abstract】 Human herpesvirus entry mediator HVEM may not only serve as the receptor to interact with LIGHT member of TNFR/TNF superfamily to deliver the negative signals,but also as the ligand for the binding with B and T lymphocyte attenu- ator(BTLA)to mediate the positive signals.To clarify this characterized and complicated regulatory effect of expression pat- terns on immunocytes and function of human HVEM molecule on T cells,human peripheral blood mononuclear cells(PBMC) were stimulated with LPS and the human T lymphocytes were activated by PHA or PMA/IM.Indirect fluorescence labeling as- say and flow cytometry analysis(FCM)were used to analyze the expression of HVEM,and MTT assay was employed to ana- lyze the proliferation of T cells.It was demonstrated that human HVEM molecule could induce a regulatory expression with an initial up-regulation and subsequent down-regulation of HVEM in CD4~+,CD8~+ T cells,and that in CD14~+ monocytes gradu- ally down-regulated,while the changes in CD19~+ B cells was not clear by stimulation with LPS.As demonstrated by the T cell proliferation reaction,the transfectant L939/LIGHT could obviously improve T cell proliferation and the secretion of IL-2 and IFN-γ.It is evident that the BTLA/HVEM signal partially mimicked by mouse anti-human BTLA can profoundly inhibit the proliferation of T cells stimulated by anti-CD3 monoclonal antibody,but suppress the secretions of cytokines IL-2,IFN-γand IL-10.更多还原