Blauvelt A, Chougnet C, Shearer G M, Katz S I
Dermatology Branch, National Cancer Institute, Bethesda, Maryland 20892-1908, USA.
J Clin Invest. 1996 Mar 15;97(6):1550-5. doi: 10.1172/JCI118578.
Decreased antigen (Ag)-specific T cell (TC) proliferation and IL-2 production are detected in all stages of HIV disease. To determine whether dendritic cell dysfunction and/or abnormal cytokine production contribute to HIV-induced immune dysregulation, we studies TC responses to recall Ags (influenza virus and tetanus toxoid) presented by Langerhans cells (LC) in six pairs of HIV-discordant identical twins, and the modulation of these responses by anti-IL-10 (alphaIL-10) mAbs and IL-12. LC from HIV+ twins induced IL-2 comparable to normal LC in cultures containing TC from uninfected twins. In contrast, IL-2 production was markedly decreased in cultures containing TC from HIV+ twins. IL-12 enhanced Ag-specific IL-2 production by TC from two patients with CD4+ counts > 600. In contrast, alphaIL-10 mAbs enhanced IL-2 production in influenza virus-stimulated cultures containing TC from two patients with CD4+ counts < 20. Thus, these findings suggest that immunologic dysfunction of dendritic cells does not contribute to impaired secondary immune responses in HIV+ individuals. Although few patients were studied, partial immune reconstitution in vitro, as demonstrated here, may help to predict those individuals who might benefit from cytokines or antibodies against cytokines as immunotherapy for HIV disease.
在HIV疾病的各个阶段均检测到抗原（Ag）特异性T细胞（TC）增殖和白细胞介素-2（IL-2）产生减少。为了确定树突状细胞功能障碍和/或细胞因子产生异常是否导致HIV诱导的免疫失调，我们研究了6对HIV不一致的同卵双胞胎中，朗格汉斯细胞（LC）呈递的回忆抗原（流感病毒和破伤风类毒素）引发的TC反应，以及抗白细胞介素-10（αIL-10）单克隆抗体和白细胞介素-12对这些反应的调节作用。在含有未感染双胞胎的TC的培养物中，来自HIV阳性双胞胎的LC诱导产生的IL-2与正常LC相当。相比之下，在含有HIV阳性双胞胎的TC的培养物中，IL-2的产生明显减少。白细胞介素-12增强了两名CD4+细胞计数>600的患者的TC产生的抗原特异性IL-2。相反，αIL-10单克隆抗体增强了两名CD4+细胞计数<20的患者的TC在流感病毒刺激的培养物中产生的IL-2。因此，这些发现表明，树突状细胞的免疫功能障碍不会导致HIV阳性个体的继发性免疫反应受损。尽管研究的患者数量很少，但此处所示的体外部分免疫重建可能有助于预测哪些个体可能从细胞因子或抗细胞因子抗体作为HIV疾病的免疫治疗中获益。
