Homsy J, Meyer M, Tateno M, Clarkson S, Levy J A
Department of Medicine, School of Medicine, University of California, San Francisco 94143.
Science. 1989 Jun 16;244(4910):1357-60. doi: 10.1126/science.2786647.
Antibodies that enhance human immunodeficiency virus (HIV) infectivity have been found in the blood of infected individuals and in infected or immunized animals. These findings raise serious concern for the development of a safe vaccine against acquired immunodeficiency syndrome. To address the in vivo relevance and mechanism of this phenomenon, antibody-dependent enhancement of HIV infectivity in peripheral blood macrophages, lymphocytes, and human fibroblastoid cells was studied. Neither Leu3a, a monoclonal antibody directed against the CD4 receptor, nor soluble recombinant CD4 even at high concentrations prevented this enhancement. The addition of monoclonal antibody to the Fc receptor III (anti-FcRIII), but not of antibodies that react with FcRI or FcRII, inhibited HIV type 1 and HIV type 2 enhancement in peripheral blood macrophages. Although enhancement of HIV infection in CD4+ lymphocytes could not be blocked by anti-FcRIII, it was inhibited by the addition of human immunoglobulin G aggregates. The results indicate that the FcRIII receptor on human macrophages and possibly another Fc receptor on human CD4+ lymphocytes mediate antibody-dependent enhancement of HIV infectivity and that this phenomenon proceeds through a mechanism independent of the CD4 protein.
在受感染个体的血液以及受感染或免疫的动物体内，已发现能增强人类免疫缺陷病毒（HIV）感染性的抗体。这些发现引发了人们对研发安全的获得性免疫缺陷综合征疫苗的严重担忧。为了探究这一现象在体内的相关性及机制，研究了外周血巨噬细胞、淋巴细胞和人成纤维样细胞中HIV感染性的抗体依赖性增强作用。针对CD4受体的单克隆抗体Leu3a以及即使高浓度的可溶性重组CD4均无法阻止这种增强作用。添加针对Fc受体III的单克隆抗体（抗FcRIII）可抑制外周血巨噬细胞中1型和2型HIV的增强作用，但与FcRI或FcRII反应的抗体则无此作用。虽然抗FcRIII无法阻断CD4 +淋巴细胞中HIV感染的增强作用，但添加人免疫球蛋白G聚集体可抑制该作用。结果表明，人巨噬细胞上的FcRIII受体以及人CD4 +淋巴细胞上可能的另一种Fc受体介导了HIV感染性的抗体依赖性增强，且这一现象通过一种独立于CD4蛋白的机制发生。
