白细胞介素12诱导T细胞凋亡对Bcl-2表达和信号分子的影响

IL-12 induces T lymphocytes underging apoptosis and affects the expression and signal conduction of Bcl-2

目的 :了解和探讨白细胞介素 12 (IL - 12 )作用于T细胞 ,活化T细胞表面的IL - 12受体 β ,诱导T细胞凋亡对Bcl- 2表达和信号转导的作用。方法 :用AnnexinV流式细胞仪检测细胞凋亡率和半定量PCR的方法测定在不同抑制剂作用下对Bcl- 2信号转导表达的影响。结果 :IL - 12在高浓度下诱导人的白血病T细胞株TIB- 15 2和人的淋巴瘤T细胞株HTB - 176及正常人T细胞的凋亡。在IL - 12处理 6h后Bcl- 2的表达明显升高 ,表达的高峰值在 2 4h ,Bcl- 2的升高不能抑制和阻碍T细胞的凋亡 ;IL - 12诱导上调T细胞Bcl- 2mRNA表达。HA10 0能促进T细胞的凋亡 ,PKC是IL - 12诱导T细胞凋亡信号转导的负性调节因子 ;AG4 90不抑制IL - 12上调的Bcl- 2mRNA表达作用 ,AG4 90阻断的Jak2通路不参与IL - 12诱导T细胞mRNA表达的信号转导及其调节 ;HA10 0 4不影响T细胞表达mRNA ,PKA通路不影响IL - 12诱导T细胞表达Bcl- 2mRNA的信号传递。结论 :Bcl- 2是凋亡介导分子之一 ,但是Bcl- 2不能阻断Fas-FasL介导的T细胞凋亡。

AIM: IL-12 acts upon T lymphocytes and activates its receptor complexes of β1/β2 ,and so IL-12 can regulate TH1/TH2 balance. Our study is aimed at IL-12-inducing apoptosis of T cells and expression and signal conduction of Bcl-2 during T cell apoptosis. METHODS: The apoptosis of T cells was detected by Annexin V staining cytometry and the expression of Bcl-2 under different inhibitors were detected by the method of semi-quantitative PCR. RESULTS: IL-12 can induce the human leukemic T cell line(TIB-152) and the human lymphoma T cell line(HTB-176) and the normal human T cells to undergo apoptosis. The Bcl-2 expression at 6 hours of treatment with IL-12 increased aparently,and reached the max at 24 hours. But IL-12 did influence Bcl-2 expression. IL-12 can induce T cells to undergo apoptosis which is characterized by early membrane changes. CONCLUSION: The inducing effect is correlated with the concentration of IL-12 and the maturation of T cells. Bcl-2 takes part in the progression of T cells' apoptosis as a apoptosis mediator.