Lyerly H K, Reed D L, Matthews T J, Langlois A J, Ahearne P A, Petteway S R, Weinhold K J
Department of Surgery, Duke University Medical Center, Durham, NC 27710.
AIDS Res Hum Retroviruses. 1987;3(4):409-22. doi: 10.1089/aid.1987.3.409.
Cytophilic antibodies which mediate antibody dependent cellular cytotoxicity (ADCC) against envelope antigens of human immunodeficiency virus (HIV) can be found in seropositive individuals. In these experiments, sera from a wide spectrum of HIV infected patients ranging from asymptomatic to overt acquired immunodeficiency syndrome (AIDS) were shown to contain high titers of antibodies that mediate ADCC. Not only did patient antibodies bind to surface expressed viral antigens and mediate ADCC against cells chronically infected with human T-lymphotropic virus type IIIB (HTLV-IIIB), but also against cells infected with the divergent HTLV-IIIRF2 and HTLV-IIIMN viral isolates. Similar results were obtained with target cells bearing purified GP 120 from HTLV-IIIB and HTLV-IIIRF2, indicating that a major portion of the activity was mediated by anti-GP 120 antibodies. Consistent with this was the ability to absorb most of the group-specific ADCC activity from the serum of an HIV infected individual using affinity columns bearing purified HTLV-IIIB GP 120. The finding that human antibodies reactive against the HIV envelope glycoprotein mediate ADCC against cells chronically infected with divergent strains of HIV will have important implications in designing rational approaches to passive and active immunotherapy.
在血清反应阳性个体中可发现能介导针对人类免疫缺陷病毒(HIV)包膜抗原的抗体依赖性细胞毒性(ADCC)的嗜细胞抗体。在这些实验中,从无症状到明显获得性免疫缺陷综合征(AIDS)的广泛HIV感染患者的血清显示含有高滴度的介导ADCC的抗体。患者抗体不仅能结合表面表达的病毒抗原,并介导针对慢性感染人T淋巴细胞白血病病毒IIIB型(HTLV-IIIB)的细胞的ADCC,还能介导针对感染不同的HTLV-IIIRF2和HTLV-IIIMN病毒分离株的细胞的ADCC。用携带来自HTLV-IIIB和HTLV-IIIRF2的纯化GP 120的靶细胞也获得了类似结果,表明大部分活性是由抗GP 120抗体介导的。与此一致的是,使用携带纯化的HTLV-IIIB GP 120的亲和柱能够从HIV感染个体的血清中吸收大部分组特异性ADCC活性。针对HIV包膜糖蛋白具有反应性的人抗体介导针对感染不同HIV毒株的慢性感染细胞的ADCC这一发现,将对设计合理的被动和主动免疫治疗方法具有重要意义。