非洲爪蟾TGF-β5和小鼠TRP-2联合免疫诱导产生抗肿瘤免疫应答  

Induction of antitumor immunity by genetic immunization with a combination of aTGF-β5 and mTRP-2

作　　者：贾正才[1] 吴玉章[1] 邹丽云[1] 万瑛[1] 吕燕波[1] 

机构地区：[1]第三军医大学基础医学部全军免疫学研究所,重庆400038

出　　处：《第三军医大学学报》2005年第3期189-191,共3页Journal of Third Military Medical University

基　　金：国家重点基础研究发展规划资助项目 ("973"项目 ) ( 2 0 0 1CB510 0 0 1) ;国家自然科学基金资助重大项目 ( 90 2 0 80 6 8)

摘　　要：目的　研究非洲爪蟾转化生长因子 β5 (aTGF β5 )基因免疫对肿瘤治疗性质粒DNA疫苗诱导抗肿瘤免疫应答的效能的影响 ,探讨所诱导免疫应答的抗肿瘤机制。方法　用aTGF β5真核表达质粒和小鼠酪氨酸酶相关蛋白 2 (mTRP 2 )真核表达质粒联合免疫野生型C5 7BL/6小鼠、CD4缺陷的C5 7BL/6小鼠和CD8缺陷的C5 7BL/6小鼠 ,于免疫前或免疫后接种黑色素瘤细胞B16F10 ,观测肿瘤生长和小鼠存活情况。结果　两种质粒联合免疫能在野生型C5 7BL/6小鼠体内诱导产生保护性和治疗性抗肿瘤免疫 ,而mTRP 2真核表达质粒单独免疫野生型C5 7BL/6小鼠及两种质粒联合免疫CD4或CD8缺陷的C5 7BL/6小鼠均不能诱导产生抗肿瘤免疫应答。结论　aTGF β5基因免疫能增强编码mTRP 2的肿瘤治疗性质粒DNA疫苗诱导抗肿瘤免疫应答的能力 ;T细胞免疫应答的诱导是抗小鼠黑色素瘤免疫应答所必需的。Objective To study the effects of genetic immunization with Xenopus laevis transforming growth factor-beta 5 (aTGF-β5) on the efficacy of plasmid DNA vaccine encoding murine tyrosinase-related protein 2 (mTRP-2) and investigate the mechanisms of tumor protection after immunization. Methods C57BL/6 wild-type mice, CD4-deficient mice, and CD8-deficient mice on the C57BL/6 background were immunized intramuscularly with a combination of aTGF-β5 and mTRP-2, and inoculated subcutaneously with B16F10 melanoma cells one day before immunization or at 7 d after immunization. Tumor growth and survival of immunized mice were investigated. Results Immunization with a combination of aTGF-β5 and mTRP-2 induced both protective and therapeutic antitumor immunity in C57BL/6 wild-type mice whereas the antitumor activity was significantly abrogated in CD4-deficient mice and CD8-deficient mice, but immunization with mTRP-2 alone did not induce antitumor immunity in C57BL/6 wild-type mice. Conclusion Genetic immunization with aTGF-β5 may enhance the effectiveness of plasmid DNA vaccine encoding mTRP-2 to elicit antitumor immunity. The antitumor activity induced by this immunization strategy may be dependent on CD4 + T lymphocytes. CD8 + cytotoxic T lymphocyte may be the major component responsible for the antitumor activity.

关 键 词：转化生长因子—β DNA疫苗 酪氨酸酶相关蛋白2 细胞毒性T淋巴细胞 肿瘤 

分 类 号：R392.11[医药卫生—免疫学] R730.5[医药卫生—基础医学]