Dressel R, Elsner L, Quentin T, Walter L, Günther E
Division of Immunogenetics, University of Göttingen, Göttingen, Germany.
J Immunol. 2000 Mar 1;164(5):2362-71. doi: 10.4049/jimmunol.164.5.2362.
Heat shock or transfection with heat shock protein 70 (Hsp70) genes has been shown to protect tumor cell lines against immune mechanisms of cytotoxicity. We have reported previously that heat shock confers resistance to CTL in the rat myeloma cell line Y3 that is Hsp70 defective. Evidence is now presented that Hsp70 is able to prevent the induction of the resistant phenotype. In Con A-stimulated lymphocytes and in lymphocyte x Y3 somatic cell hybrid clones a severe, non-Hsp70-inducing heat shock elicits resistance to CTL in contrast to a heat shock that results in Hsp70 expression. Thus, Hsp70 expression appears to be negatively associated with the development of resistance. Furthermore, loading of Y3 cells with recombinant Hsp70 protein before heat shock is able to prevent resistance. Because apoptosis induced in Y3 cells by heat shock is not affected, Hsp70 appears to interfere selectively with the CTL-induced lethal pathway that is found to be calcium but not caspase dependent. It is suggested that after heat shock Hsp70 enhances the CTL-induced apoptotic pathway by chaperoning certain proteins in the target cell that are involved in the execution of cell death. Thus, although shown to confer protection against many cytotoxic mechanisms, Hsp70 does not appear to be generally cytoprotective. This observation could also be of relevance when interpreting the effectiveness of tumor immunity.
热休克或用热休克蛋白70（Hsp70）基因转染已被证明可保护肿瘤细胞系免受细胞毒性免疫机制的影响。我们之前报道过热休克可使Hsp70缺陷的大鼠骨髓瘤细胞系Y3对细胞毒性T淋巴细胞（CTL）产生抗性。现在有证据表明Hsp70能够阻止抗性表型的诱导。在刀豆蛋白A刺激的淋巴细胞以及淋巴细胞与Y3体细胞杂交克隆中，与导致Hsp70表达的热休克相反，严重的、不诱导Hsp70的热休克会引发对CTL的抗性。因此，Hsp70的表达似乎与抗性的发展呈负相关。此外，在热休克前用重组Hsp70蛋白加载Y3细胞能够阻止抗性的产生。由于热休克诱导Y3细胞凋亡不受影响，Hsp70似乎选择性地干扰了CTL诱导的致死途径，该途径被发现是钙依赖性而非半胱天冬酶依赖性的。有人提出，热休克后Hsp70通过陪伴靶细胞中某些参与细胞死亡执行的蛋白质来增强CTL诱导的凋亡途径。因此，尽管Hsp70已被证明可抵御多种细胞毒性机制，但它似乎并非普遍具有细胞保护作用。这一观察结果在解释肿瘤免疫的有效性时也可能具有相关性。
