Zarling J M, Ledbetter J A, Sias J, Fultz P, Eichberg J, Gjerset G, Moran P A
Oncogen, Seattle, WA 98121.
J Immunol. 1990 Apr 15;144(8):2992-8.
It has been suggested that autoimmune phenomena contribute to the depletion of CD4+ T cells and the development of AIDS in HIV-1 infected humans based, in part, on observations that some HIV-1-infected humans have autoantibodies reactive with Ag expressed on uninfected CD4+ cells. In this study, 11 of 14 asymptomatic HIV-1-infected homosexuals and hemophiliacs, but none of 17 uninfected homosexuals or heterosexuals, were found to have cytotoxic lymphocytes in blood that can lyse uninfected CD4+ T cells from humans and chimpanzees but not human B lymphoblastoid cells or mouse T cells. The cytotoxic PBL were concluded to be CTL rather than NK cells, with the phenotype being CD3+, TCR-1 alpha beta+, CD8+, CD4-, CD16- based on findings that PBL-mediated lysis of uninfected CD4+ cells was 1) blocked by a mAb to CD3, which inhibits CTL but not NK activity; 2) diminished by treatment of PBL with a mAb to CD8 and C, but not by treatment with mAb to CD4 or CD16 and C; and 3) blocked by mAb WT31 directed against the TCR-1 alpha beta. In contrast, PBL from HIV-1-infected chimpanzees, which to date have not developed AIDS, lacked detectable CTL lytic for uninfected CD4+ cells.
有人提出，自身免疫现象在一定程度上导致了HIV-1感染人类中CD4+T细胞的耗竭和艾滋病的发展，这部分基于一些观察结果，即一些HIV-1感染的人类具有与未感染CD4+细胞上表达的抗原发生反应的自身抗体。在本研究中，14名无症状HIV-1感染的同性恋者和血友病患者中有11人，但17名未感染的同性恋者或异性恋者中无人被发现血液中有可裂解来自人类和黑猩猩的未感染CD4+T细胞但不能裂解人类B淋巴母细胞或小鼠T细胞的细胞毒性淋巴细胞。基于以下发现，细胞毒性外周血淋巴细胞被判定为细胞毒性T淋巴细胞（CTL）而非自然杀伤细胞（NK细胞），其表型为CD3+、TCR-1αβ+、CD8+、CD4-、CD16-：1）未感染CD4+细胞的外周血淋巴细胞介导的裂解被抗CD3单克隆抗体阻断，该抗体抑制CTL活性但不抑制NK活性；2）用抗CD8和补体处理外周血淋巴细胞可减少裂解，而用抗CD4或CD16和补体处理则无此效果；3）针对TCR-1αβ的单克隆抗体WT31可阻断裂解。相比之下，迄今为止尚未发展为艾滋病的HIV-1感染黑猩猩的外周血淋巴细胞缺乏可检测到的对未感染CD4+细胞具有裂解作用的CTL。
