Role of nitric oxide in heat shock protein induced apoptosis of γδT cells

被引:14
作者
Atre, Nilangi
Thomas, Loui
Mistry, Rajesh
Pathak, Kumar
Chiplunkar, Shubhada
机构
[1] Tata Mem Hosp, ACTREC, Navi Mumbai 410208, India
[2] Tata Mem Hosp, Dept Surg Oncol, Bombay 400012, Maharashtra, India
关键词
heat shock proteins; oral cancer; gamma delta T lymphocytes; apoptosis; nitric oxide;
D O I
10.1002/ijc.21966
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Activation induced cell death (AICD) has been proposed to serve as a mechanism to limit T lymphocyte proliferation induced by antigenic stimulation. Heat shock proteins (hsp60 and hsp70) expressed on oral tumor cells serve as ligands for peripheral blood gamma delta T lymphocytes. Tumor cell lysis by gamma delta T lymphocytes is mediated via recognition of hsp expressed on tumor cells. In the present study, we report that upon stimulation with hsp, gamma delta T lymphocytes isolated from oral cancer patients undergo AICD as confirmed by DNA ploidy, annexin V staining and confocal microscopy. In co-cultures of gamma delta T lymphocytes and tumor cells, addition of antihsp60 and antihsp70 MAb, but not anti-Fas MAb (ZB4), inhibited DNA fragmentation of gamma delta T lymphocytes. Flow cytometric analysis revealed a down regulation of Fas expression on gamma delta T lymphocytes upon incubation with hsp60 and hsp70. Increased expression of iNOS was observed in hsp-stimulated gamma delta T lymphocytes. Addition of monomethyl L-arginine monoacetate, competitive inhibitor of NOS, inhibited nitric oxide (NO) production and apoptosis of gamma delta T lymphocytes induced by hsp60 and hsp70. The NO-induced apoptosis of gamma delta T lymphocytes involves activation of caspase-9 and loss of mitochondrial membrane potential. The present study explains a novel strategy adopted by tumor cells to evade immune recognition by gamma delta T lymphocytes. (c) 2006 Wiley-Liss, Inc.
引用
收藏
页码:1368 / 1376
页数:9
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