4-1BBL介导的逆向信号对人外周血T细胞体外活化的调节作用

The reverse signal mediation of regulates activation of human peripheral blood T cell by 4-1BBL in vitro

目的探讨表达于活化T细胞上的4-1BBL分子对T细胞的调节作用及可能机制。方法鼠抗人4-1BBL单克隆抗体1F1加入CD3单抗联合CD28单抗激发的T细胞培养体系。细胞计数分析T细胞的增殖;PI/AnnexinⅤ双染法分析T细胞的凋亡;ELISA法测定培养上清中细胞因子的分泌水平;流式细胞仪分析T细胞的表型。结果单抗1F1能够有效地抑制活化T细胞的体外增殖并诱导其凋亡,同时单抗1F1还可抑制活化T细胞分泌IL-2和IFN-γ及上调T细胞表面CD95和PD-1分子的表达。结论在T细胞活化过程中,活化T细胞表达的4-1BBL分子通过逆向信号抑制其细胞因子的分泌和上调负性调控分子,进而抑制T细胞的过度活化和下调T细胞介导的免疫应答。

Objective To analyze the role of 4-1BBL, expressed in the regulation of human peripheral blood T cell activation. Methods Apoptotic T cells were evaluated by propidium iodide uptake and Annexin V binding. Cytokine concentrations in supernatants were determined by ELISA. Phenotypic analyses were performed with direct immunofluorescence techniques in a FACS. Reultss McAb 1F1 inhibited T cell proliferation and induced T cells apoptosis. In addition, McAb 1F1 suppressed the secretion of IL-2 and IFN-γ, and upregulated the expression of CD95 and PD-1.Conclusion 4-1BBL reverse signal prevent T cell activation and downregulate immune responses mediated by T cell via inhibiting secretion of cytokines and uprregulating negative costimulatory molecule.