摘要目的 为了进一步增强HIV DNA疫苗的免疫反应,本研究将IL-17作为HIV DNA疫苗的分子佐剂免疫小鼠,旨在探讨IL-17对HIVDNA疫苗诱导体液和细胞免疫应答的影响.方法 将小鼠IL-17构建到真核表达载体,与HW-1膜蛋白DNA疫苗pGX-Env联合免疫BALB/c小鼠;分别在第0、2周进行免疫,在第4周检测T淋巴细胞增殖指数、抗-Env IgG、细胞因子表达水平和体内细胞毒性T淋巴细胞杀伤作用(CTL)等免疫学指标.结果 IL-17能够增强HIV DNA疫苗的特定免疫反应.与单注射疫苗组相比,IL-17作为佐剂组的T细胞增殖、抗体水平和CD4~+T细胞分泌IFN-γ、IL-4和IL-17的表达均无明显增强,但对CD8~+T细胞分泌IFN-γ的表达和体内CTL的效果影响明显(P<0.05).结论 IL-17作为分子佐剂不足以影响Th细胞分化,然而却能够增强特异性CD8~+T细胞中IFN-γ的表达,尤其是增强体内CTL反应.此结果为增强艾滋病DNA疫苗CD8~+T细胞活性和用于艾滋病的治疗提供了一个新的思路.

abstractsObjective To investigate IL-17 as adjuvant effect on the humoral and cellular immune responses to HIV DNA vaccine by immunizing mice with HIV DNA vaccine plus IL-17. Methods We immunized the BALB/c mice with pGX-Env alone, or with pcDNA3-IL-17 by intramuscular injection. The immunization was performed on week 0, 2. The concentration of the anti-Env IgG, the stimulated index of T lymphocyte proliferation, and the expression of IFN-γ, IL-4 and IL-17 in CD4~+T cell and IFN-γ in CD8~+ T cell, specific in vivo cytotoxic T lymphocyte (CTL) activity were detected at week 4. Results We show here that IL-17 as a molecular adjuvant with the HIV DNA vaccine, pGX-Env, can enhance immune responses. Interestingly, IL-17 has no adjuvant effect on the responses for T cell proliferation, antibody production and expressions of IFN-γ, IL-4 and IL-17 in CD4~+ T cells, but rather on the up-regulation of IFN-γ in CD8~+ T cells and CTL in vivo significantly(P<0.05). Conclusion The data suggest that IL-17 as the molecular adjuvant may not effect the development and differentiation of CD4~+ Th cells, but directly affect on the CD8~+ T cell functions. The novel functionality of IL-17 on adaptive immunity may lead to develop effecfive HIV DNA vaccination targeted to potentiate the CD8~+ T cell functions.