全反式维甲酸对基因免疫应答的调节作用

The effects of ATRA on immune response induced by gene immunization

目的 研究全反式维甲酸 (ATRA)对TR4 2 1 hCGβ质粒基因免疫诱生的特异性细胞免疫与体液免疫应答的调节作用。方法 肌肉注射重组质粒TR4 2 1 hCGβDNA(每只鼠 5 0 μg 10 0 μl)初次免疫小鼠 ,以灌胃的方式给予ATRA ,并以灌溶剂和TR4 2 1质粒免疫为对照 ;3周与 6周后经同样的方式加强免疫各组小鼠 ,采用ELISA方法对基因免疫小鼠血清中IgG抗体水平进行动态观察 ,分析小鼠血清中IgG抗体亚类 ;3H TdR掺入法测定特异性细胞增殖和细胞杀伤功能。结果 ELISA结果表明 ,TR4 2 1 hCGβ质粒基因免疫诱生较高的抗hCGβ抗体水平 ,ATRA增强TR4 2 1 hCGβ质粒基因免疫诱生的抗hCGβ特异性IgG抗体水平并且伴随IgG2a IgG1显著性降低 ;TR4 2 1 hCGβ质粒基因免疫诱生较强的淋巴细胞增殖活性和CTL活性 ,ATRA抑制TR4 2 1 hCGβ质粒基因免疫诱生的特异性细胞增殖和细胞杀伤功能。结论 ATRA促进基因免疫诱生的TH2免疫应答 ,抑制TH1型免疫应答 ,为改变基因免疫诱生的特异性免疫应答类型提供了一条新的途径。

Objective To investigate the effects of all-trans retinoic acid(ATRA) on the immune response induced by plasimd of TR421-hCGβ gene immunization. Methods BALB/c mice were primed by i.m. gene immunization with recombinant plasmid TR421-hCGβ coding for hCGβ and mock DNA on day 0 and ATRA was orally administered. The mice were boosted by the same way 3 and 6 weeks post-priming. Serum IgG collected at indicated times from each group was determined by ELISA. Specific lympho-proliferation versus hCGβ was detected by [ 3H]-Thymidine incorporation assay with inactivated SP2/0-hCGβ cells as specific stimulatory antigen. CTL activity of the splenocytes derived from the immunized mice was measured by [ 3H]-Thymidine release assay. Results Specific anti-hCGβ IgG antibody response was elicited in groups primed with plasmids TR421-hCGβ. ATRA enhanced the levels of IgG with IgG2a/IgG1 ratio decreased. A high-leveled and specific lympho-proliferation against inactivated SP2/0-hCGβ cells was observed in TR421-hCGβ immunized mice. A strong cytotoxic activity against SP2/0-hCGβ in TR421-hCGβ immunized mice was found. ATRA inhibited the specific lympho-proliferation and cytotoxic activity induced by gene immunization. Conclusion ATRA improves T_H2 type immune response and reduces T_H1 type immune response induced by gene immunization.