细胞毒性T细胞
CTL公司*
细胞凋亡
Fas配体
生物
CD8型
受体
癌症研究
T细胞
程序性细胞死亡
单克隆抗体
免疫学
细胞生物学
抗原
抗体
化学
免疫系统
生物化学
体外
作者
Asma Gati,Nadia Guerra,Catherine Gaudin,Sylvie Da Rocha,Bernard Escudier,Yann Lécluse,Ali Bettaı̈eb,Salem Chouaı̈b,Anne Caignard
出处
期刊:PubMed
日期:2003-11-01
卷期号:63 (21): 7475-82
被引量:40
摘要
Renal cell carcinoma-infiltrating lymphocytes express killer cell immunoglobulin-like receptors (KIRs) that inhibit antitumor CD8+ T-cell functions and may contribute to local self-tolerance. In the present study, to better examine the functional consequences of KIR engagement on CTL-tumor interactions, we investigated the influence of KIR2DL1/CD158a on CTL survival. We show that both KIR+ and KIR- antigen-specific CTLs express Fas and Fas ligand and were susceptible to activation-induced cell death (AICD) triggered by coated anti-CD3 monoclonal antibodies. In KIR+ CTLs, anti-CD158a monoclonal antibodies partially inhibited anti-CD3-induced AICD. Interestingly, T-cell receptor activation by cognate tumor cells induced apoptosis in KIR+ CTLs but not in KIR- CTLs. In addition, co-engagement of T-cell receptors and KIRs by tumor cells decreased tumor-mediated CTL apoptosis. Blocking the interaction of KIR/HLA-Cw4 resulted in the restoration of tumor-induced AICD. Most importantly, our data indicate that KIR engagement affected two proximal events of Fas signaling pathway, a sustained c-FLIP-L induction and a decrease in caspase 8 activity. These studies provide evidence that tumor cells selectively favor the local persistence of nonfunctional KIR+ CTLs by promoting their survival.
科研通智能强力驱动
Strongly Powered by AbleSci AI