Chenciner N, Michel F, Dadaglio G, Langlade-Demoyen P, Hoffenbach A, Leroux A, Garcia-Pons F, Rautmann G, Guy B, Guillon J M
Laboratoire de Biologie et Immunologie Moléculaires des Rétrovirus, Institut Pasteur, Paris, France.
Eur J Immunol. 1989 Sep;19(9):1537-44. doi: 10.1002/eji.1830190904.
The human immunodeficiency virus type 1 (HIV-1) induces a strong cytotoxic T lymphocyte (CTL) response in humans following infection. HIV-specific CTL can be detected directly in the blood and lungs of infected patients, and can be expanded in vitro by stimulation with autologous HIV-infected lymphoblasts. Furthermore, CTL specific for HIV envelope glycoprotein gp160 have been obtained in mice by immunization with recombinant vaccinia virus (VV) that carry the HIV env gene. In this study, we show that mice also produce strong CTL responses to gag and nef proteins following immunization with VV recombinants, thus providing a convenient model system to study T lymphocyte immunity to defined HIV antigens. To determine the specificity of circulating HIV-immune CTL in humans, a panel of doubly transfected mouse P815 tumor cells was produced which express the human HLA-A2 or HLA-A3 transplantation antigen gene and one HIV-1 gene (env, gag or nef). Using these cells as targets to CTL, we show that HIV-infected humans carry co-existing CTL sub-populations of different specificities. Each subpopulation appears to vary in intensity among different individuals. Surprisingly, CTL specific for regulatory, non-structural nef protein appear to be a major constituent of the human immune response to HIV.
人类免疫缺陷病毒1型（HIV-1）感染人体后会引发强烈的细胞毒性T淋巴细胞（CTL）反应。在受感染患者的血液和肺部可直接检测到HIV特异性CTL，并且通过用自体HIV感染的淋巴母细胞刺激可在体外使其扩增。此外，通过用携带HIV env基因的重组痘苗病毒（VV）免疫，已在小鼠中获得了针对HIV包膜糖蛋白gp160的CTL。在本研究中，我们表明小鼠在用VV重组体免疫后对gag和nef蛋白也产生强烈的CTL反应，从而提供了一个方便的模型系统来研究针对特定HIV抗原的T淋巴细胞免疫。为了确定人类循环中HIV免疫CTL的特异性，制备了一组双转染的小鼠P815肿瘤细胞，其表达人类HLA-A2或HLA-A3移植抗原基因以及一个HIV-1基因（env、gag或nef）。以这些细胞作为CTL的靶标，我们表明HIV感染的人类携带不同特异性的共存CTL亚群。不同个体中每个亚群的强度似乎有所不同。令人惊讶的是，针对调节性非结构nef蛋白的CTL似乎是人类对HIV免疫反应的主要组成部分。
