人共信号分子HVEM在外周血PBMC表达特性及其对T细胞的生物学作用

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。

Preliminary analysis of the regulatory expression and inhibitory function of the human herpesvirus entry mediator HVEM

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.