Clerici M, Lucey D R, Berzofsky J A, Pinto L A, Wynn T A, Blatt S P, Dolan M J, Hendrix C W, Wolf S F, Shearer G M
Experimental Immunology Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892.
Science. 1993 Dec 10;262(5140):1721-4. doi: 10.1126/science.7903123.
Peripheral blood mononuclear cells (PBMCs) from many asymptomatic individuals infected with human immunodeficiency virus-type 1 (HIV) are unresponsive as measured by in vitro T cell proliferation and interleukin-2 (IL-2) production to influenza virus and synthetic peptides of HIV envelope (Env). Strong influenza virus- and Env-stimulated IL-2 responses and T cell proliferation were restored when cultures were stimulated in the presence of IL-12. Interferon-gamma production by PBMCs from HIV seropositive (HIV+) patients was also restored with IL-12. Furthermore, in vitro antigen-specific production of IL-2 and proliferation of PBMCs from HIV- donors were suppressed by antibody to IL-12, but were not enhanced by addition of exogenous IL-12. Thus, IL-12 may be limiting in PBMCs from HIV+ but not HIV- individuals. These findings demonstrate that IL-12 can restore HIV-specific cell-mediated immunity in vitro in HIV-infected individuals and suggest a potential use of IL-12 in augmenting the diminished immunologic functions associated with HIV infection.
通过体外T细胞增殖和白细胞介素-2（IL-2）产生情况来衡量，许多感染1型人类免疫缺陷病毒（HIV）的无症状个体的外周血单个核细胞（PBMC）对流感病毒和HIV包膜（Env）合成肽无反应。当在IL-12存在的情况下刺激培养物时，流感病毒和Env刺激的强烈IL-2反应以及T细胞增殖得以恢复。HIV血清阳性（HIV+）患者的PBMC产生的干扰素-γ也可通过IL-12恢复。此外，来自HIV阴性（HIV-）供体的PBMC的体外抗原特异性IL-2产生和增殖受到抗IL-12抗体的抑制，但添加外源性IL-12并未增强其反应。因此，IL-12在HIV+个体而非HIV-个体的PBMC中可能是受限的。这些发现表明，IL-12可以在体外恢复HIV感染个体中HIV特异性细胞介导的免疫，并提示IL-12在增强与HIV感染相关的免疫功能减弱方面具有潜在用途。
