IL-12基因对HIV-1核酸疫苗诱导的免疫应答的影响

Interleukin-12 Gene Modulates Immune Responses Induced by HIV-1 Nucleic Acid Vaccine

研究白细胞介素 12(IL 12)基因对HIV 1核酸疫苗诱导免疫应答的影响,以探求治疗性 HIV 1 核酸疫苗的新策略。将 pCI neoGAG联合白细胞介素 12基因或者 pCI neoGAG单独免疫 Balb/c小鼠,通过 ELISA检测免疫小鼠的特异性抗体和 IFN γ,通过MTT实验检测免疫小鼠脾淋巴细胞增殖实验,通过乳酸脱氢酶(LDH)实验检测小鼠特异性细胞毒性T淋巴细胞(CTL)反应。与 pCI neoGAG免疫组比较,pCI neoGAG联合白细胞介素 12基因免疫组小鼠血清的抗 HIV 1p24 抗体滴度降低,有显著性差异(P< 0. 01);而与 pCI neoGAG 免疫组比较, pCI neoGAG联合白细胞介素 12基因免疫组小鼠血清的 IFN γ升高,有显著性差异(P<0.01);pCI neoGAG联合白细胞介素 12基因免疫组小鼠的脾淋巴细胞增殖实验刺激指数(SI)以及特异性 CTL活性均高于 pCI neoGAG免疫组,有显著性差异(P<0.01)。因此,白细胞介素 12基因基因联合HIV 1核酸疫苗免疫小鼠,可能增强特异性Th1细胞和CTL反应,白细胞介素 12基因对体液免疫有抑制作用。

To investigate the effect of interleukin-12 DNA immunization on immune responses induced by HIV-1 nucleic acid vaccine(DNA vaccine)and to explore new strategies for therapeutic HIV-1 DNA vaccine, Balb/c mice were immunized with pCI-neoGAG alone or co-administered with the DNA encoding for interleukin-12 (IL-12).Their sera were collected for analyzing anti-HIV antibody and IFN-γ by ELISA , and splenocytes were isolated for detecting antigen-specific lymphoproliferative responses and specific CTL response by MTT assay and LDH assay respectively.Our research showed that the anti-HIV antibody titers of mice co-immunized with pCI-neoGAG and the DNA encoding for interleukin-12 (IL-12) were lower than that of mice immunized with pCI-neoGAG alone(P<0.01); In contrast ,the IFN-γ level of mice co-immunized with pCI-neoGAG and the DNA encoding for interleukin-12 was higher than that of mice immunized with pCI-neoGAG alone(P<0.01).Furthermore, compared with mice injected with pCI-neoGAG alone, the specific CTL cytotoxity activity and antigen-specific lymphoproliferative responses of mice immunized with pCI-neoGAG and the DNA encoding for interleukin-12 were significantly enhanced respectively (P<0.01).Thus,the DNA encoding for interleukin-12 together with HIV nucleic acid vaccine may enhance specific Th-1 responses and cellular immune responses elicited in mice. However, the DNA encoding for interleukin-12 may down-regulate the humoral responses.