Augmentation of MHC class I antigen presentation via heat shock protein expression by hyperthermia
Augmentation of MHC class I antigen presentation via heat shock protein expression by hyperthermia
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DOI：
10.1007/s00262-001-0233-7
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发表时间：
2001-12-01
影响因子：
5.8
通讯作者：
Kobayashi, T
中科院分区：
文献类型：
--
作者：
Ito, A;Shinkai, M;Kobayashi, T
热休克蛋白被认为是免疫反应的重要参与者。在这项研究中，我们证明了MHC I类抗原的细胞表面呈递随着热休克蛋白70 （HSP70）表达的增加而增加，热疗增强了大鼠T-9胶质瘤细胞的免疫原性。体外43℃热处理1 h后，T-9细胞生长抑制24 h，随后恢复正常生长。HSP70表达量在加热后24 h达到最大值。流式细胞术分析显示，加热细胞表面MHC I类抗原显著增加。MHC I类表面表达在加热24 h后开始增强，加热48 h后达到最大值。其他免疫介质，如细胞内粘附分子-1 （ICAM-1）和MHC II类抗原的表达没有增加。在免疫活性同基因大鼠（F344）的体内实验中，加热后的T-9细胞的生长明显受到抑制，MHC I类抗原表面表达增加，而裸大鼠（F344/N Jcl-rnu）的T-9细胞逐渐生长。此外，与未免疫（仅注射PBS）大鼠或注射未加热T-9细胞的大鼠淋巴细胞相比，注射加热T-9细胞的大鼠脾淋巴细胞对T-9细胞表现出特异性的细胞毒性。这些结果表明，HSP70是肿瘤细胞免疫原性的重要调节剂，肿瘤细胞高温处理可通过表达HSP70诱导宿主抗肿瘤免疫。这些结果可能有助于进一步开发基于热疗的新型癌症免疫疗法。
Heat shock proteins are recognized as significant participants in immune reactions. In this study, we have demonstrated that the cell surface presentation of MHC class I antigen was increased in tandem with increased heat shock protein 70 (HSP70) expression and the immunogenicity of rat T-9 glioma cells was enhanced by hyperthermia. T-9 cells showed growth inhibition for 24 h after the heat treatment at 43 degreesC for 1 h in vitro, but then resumed a normal growth rate. HSP70 expression reached a maximum at 24 h after heating. Flow cytometric analysis revealed a significant increase in MHC class I antigen on the surface of the heated cells. The augmentation of MHC class I surface expression started 24 h after heating and reached a maximum 48 h after heating. The expression of other immunologic mediators, such as intracellular adhesion molecule-1 (ICAM-1) and MHC class II antigens, did not increase. In an in vivo experiment using immunocompetent syngeneic rats (F344), growth of the heated T-9 cells, with augmentation of MHC class I antigen surface expression, was significantly inhibited, while the cells grew progressively in nude rats (F344/N Jcl-rnu). Furthermore, compared with lymphocytes from non-immunized (PBS only injection) rats or rats injected with non-heated T-9 cells, the splenic lymphocytes of the rats in which the heated T-9 cells were injected displayed specific cytotoxicity against T-9 cells. These results suggest that HSP70 is an important modulator of tumor cell immunogenicity, and that hyperthermic treatment of tumor cells can induce the host antitumor immunity via the expression of HSP70. These results may benefit further efforts on developing novel cancer immunotherapies based on hyperthermia.