Michel F, Hoffenbach A, Langlade-Demoyen P, Guy B, Girard M, Lecocq J P, Wain-Hobson S, Kieny M P, Plata F
Laboratoire de Biologie et d'Immunologie Moléculaires des Rétrovirus, Institut Pasteur, Paris, France.
Eur J Immunol. 1988 Dec;18(12):1917-24. doi: 10.1002/eji.1830181208.
Infection by the human immunodeficiency virus (HIV) induces T cell immunity in humans, chimpanzees and macaques. The protective value of this immune response is not clear. We have consequently developed a murine experimental system to study HIV-specific CD4 and CD8 T lymphocyte immunity in vitro and in vivo. BALB/c, DBA/2 and C3H/He mice were immunized with vaccinia virus (VV) recombinant VV-11.39 which expresses the gp160 glycoprotein of HIV-1. Primary and secondary cytotoxic T lymphocyte response to HIV were detected with histocompatible mouse target cells transfected with the HIV-1 env gene. Killer cells were positive for the Thy-1 and Ly-2 (CD8) T cell markers, and were restricted by class I H-2 histocompatibility antigens. Immunological memory specific for HIV-1 envelope antigens was clearly induced by vaccination with VV-11.39:spleen cells from mice vaccinated 4 weeks or more prior to assay generated CD4 and CD8 T lymphocyte responses following stimulation in vitro with HIV envelope antigens. The intensity of these responses increased with consecutive vaccinations, indicating that HIV-specific precursor T cell pools were progressively amplified. Finally, DBA/2 mice vaccinated with VV-11.39 developed protective immunity against a syngeneic tumor which expresses HIV-1 env antigens, leading to accelerated tumor rejection and increased survival.
人类免疫缺陷病毒(HIV)感染可在人类、黑猩猩和猕猴中诱导T细胞免疫。这种免疫反应的保护价值尚不清楚。因此,我们开发了一种小鼠实验系统,用于在体外和体内研究HIV特异性CD4和CD8 T淋巴细胞免疫。用表达HIV-1 gp160糖蛋白的痘苗病毒(VV)重组体VV-11.39对BALB/c、DBA/2和C3H/He小鼠进行免疫。用转染了HIV-1 env基因的组织相容性小鼠靶细胞检测对HIV的初次和二次细胞毒性T淋巴细胞反应。杀伤细胞对Thy-1和Ly-2(CD8)T细胞标志物呈阳性,且受I类H-2组织相容性抗原限制。用VV-11.39接种疫苗可明显诱导对HIV-1包膜抗原的免疫记忆:在检测前4周或更长时间接种疫苗的小鼠的脾细胞,在体外用HIV包膜抗原刺激后产生CD4和CD8 T淋巴细胞反应。这些反应的强度随着连续接种而增加,表明HIV特异性前体T细胞库逐渐扩大。最后,用VV-11.39接种疫苗的DBA/2小鼠对表达HIV-1 env抗原的同基因肿瘤产生了保护性免疫,导致肿瘤排斥加速和生存期延长。