TJU103联合CTLA4-Ig对T细胞表型和分泌细胞因子的影响

Effect of Combined Use of TJU103 and CTLA4-Ig on Phenotypes of T Cells and Secretion of Cytokines

本研究应用HLA半相合供、受者间单向混合淋巴细胞培养 (MLC )体系 ,体外检测了联合应用TJU10 3和CTLA4 Ig对供者T细胞增殖以及表型和分泌细胞因子的影响。结果显示 ,单独应用TJU10 3和CTLA4 Ig均能够降低T细胞的增殖活性 ,二者联合应用具有明显的协同抑制增殖效应 ,并能够使CD4 + CD6 9+ /CD8+ CD6 9+ 比值降低 ,Th1型细胞因子 (TNF α ,IFN γ )分泌减少 ,Th2型细胞因子 (IL 4 )分泌增加。提示TJU10 3和CTLA4 Ig联合应用能够阻断供者T细胞激活的抗原和共刺激双信号通路 ,抑制T细胞的增殖活性 ,使CD4 + CD6 9+ /CD8+ CD6 9+ 比值降低 ,并能够调节Th细胞分化 ,诱导Th细胞免疫偏离 ,使辅助性T细胞更多地向Th2细胞方向分化 ,可以作为一条预防临床HLA半相合造血干细胞移植重度移植物抗宿主病 (GVHD )

To investigate the effect of combined use of TJU103 and CTLA4-Ig on phenotypes of T cells and secretion of cytokines. The proliferation,phenotypes,and secretions of TNF-α, IFN-γ and IL-4 of the antigen-induced T cells after combined stimulation with TJU103 and CTLA4-Ig were determined by means of MTT assay,FACS analysis and ELISA assay. It was found that the combined use of TJU103 and CTLA4-Ig showed a markedly and synergetically inhibitory effect on the proliferation of T cells,although TJU103 or CTLA4-Ig alone could also depress the proliferation of T cells. In addition,the ratio of CD4 +CD69 +/CD8 +CD69 + decreased,and the secretion of Th1-type cytokines (TNF-α,IFN-γ) decreased with an enhanced production of Th2-type cytokine(IL-4). These data suggest that the combined use of TJU103 and CTLA4-Ig can block the co-stimulatory pathway,regulate the differentiation of Th cells and induce the immune shift of Th cells. This may provide a new approach to prevent the development of GVHD in case of semimatched transplantation.