ICOS通过Survivin维持T细胞分裂及存活

有关T细胞共刺激分子信号转导方面的研究远落后于其功能研究,为探讨T细胞活化后诱导表达的共刺激分子ICOS(induciblecostimulate)维持T细胞存活、抑制活化后T细胞凋亡的作用是否与survivin相关,利用survivin重组腺病毒感染活化但不提供共刺激信号的T淋巴细胞,或者在活化后提供ICOS信号的条件下人工给予优势抑制survivin突变基因,CCK-8及TUNEL法分别检测活化晚期上述T细胞存活及凋亡情况.结果显示,T细胞活化后2～6天,ICOS抗体刺激可以明显增强survivin表达,survivin可维持无ICOS信号的T细胞存活减少其凋亡,突变型survivin在ICOS信号存在下抑制T细胞存活使其凋亡增加.结果提示,活化后表达的共刺激分子ICOS通过survivin维持T细胞分裂和存活.

ICOS Regulate Survivin Expression and Sustain T Cell Survival

To study whether the late-acting co-stimulatory molecules ICOS can suppress the apoptosis and sustain the survival and proliferation of T cells through the survivin pathway, ICOS signals deficient T-cells were infected with adenovirus carried survivin gene, other T-cells were given ICOS co-stimulatory signals, then infected with adenovirus carried dominant-negative mutant survivin gene. Apoptosis and proliferation were determined by TUNEL and CCK-8 respectively. The results show that engagement of ICOS signal increased the expression level of survivin significantly. Survivin can sustain co-stimulatory deficient T cells survival and suppress the apoptosis. Mutant survivin inhibits ICOS signal positive T cells survival and increase its apoptosis. Late-acting co-stimulatory molecules ICOS can suppress the apoptosis and sustain the survival of T cells through the survivin pathway.