Francis M L, Meltzer M S
Department of Cellular Immunology, Walter Reed Army Institute of Research, Rockville, MD 20850.
J Immunol. 1993 Aug 15;151(4):2208-16.
IFN-alpha is in plasma of HIV-1 infected patients during early and late-stage disease and may play a role in control of virus replication. The stimulus for IFN-alpha production, the cells that produce this cytokine, and the effectiveness of this IFN-alpha response for control of virus infection are not yet defined. Culture fluids from freshly isolated PBMC of HIV-1 seronegative donors contained high levels of IFN-alpha after exposure to 100 to 1000 infectious HIV-1 particles per culture. Levels of IFN-alpha induced by HIV-1 were directly dependent on the number of monocytes in cell preparations: No IFN-alpha was detected from T cell-enriched PBMC. In monocyte cultures, induction of IFN-alpha by HIV-1 was relatively specific: Levels of IL-1 beta, IL-6, IFN-gamma, and TNF-alpha remained at baseline. Capacity of HIV-1 virions to induce IFN-alpha was not dependent on virus replication. IFN-alpha was induced by (a) heat-inactivated HIV-1, (b) virions from 8E5 cells, a cell line that releases noninfectious HIV-1, (c) HIV-1-infected cells fixed in paraformaldehyde, and (d) T cell-tropic HIV-1 that binds to but does not infect monocytes. Capacity of HIV-1 virions and HIV-1 infected cells to induce IFN-alpha was completely inhibited by soluble rCD4 or mAb against CD4 or gp120. Antibodies against CD4, however, did not induce monocytes to produce IFN-alpha. HIV-1-induced IFN-alpha production was inhibited by antibodies against both V3 loop determinants and the CD4 binding site of gp120. Further, sera and purified immunoglobulin from HIV-1 infected patients also inhibited HIV-1-induced IFN-alpha production. These observations suggest that potentially protective antiviral responses associated with IFN-alpha production in HIV-1 infected patients are inhibited by the development of antibodies against gp120.
在HIV-1感染患者疾病的早期和晚期，血浆中均存在α干扰素，其可能在控制病毒复制中发挥作用。α干扰素产生的刺激因素、产生这种细胞因子的细胞以及这种α干扰素反应对控制病毒感染的有效性尚未明确。来自HIV-1血清阴性供者新鲜分离的外周血单核细胞（PBMC）的培养液在每培养物暴露于100至1000个感染性HIV-1颗粒后含有高水平的α干扰素。HIV-1诱导的α干扰素水平直接取决于细胞制剂中单核细胞的数量：从富含T细胞的PBMC中未检测到α干扰素。在单核细胞培养物中，HIV-1诱导α干扰素相对具有特异性：白细胞介素-1β、白细胞介素-6、γ干扰素和肿瘤坏死因子-α水平保持在基线。HIV-1病毒体诱导α干扰素的能力不依赖于病毒复制。α干扰素可由以下物质诱导：（a）热灭活的HIV-1；（b）来自8E5细胞系（释放无感染性HIV-1的细胞系）的病毒体；（c）用多聚甲醛固定的HIV-1感染细胞；（d）与单核细胞结合但不感染单核细胞的嗜T细胞HIV-1。HIV-1病毒体和HIV-1感染细胞诱导α干扰素的能力被可溶性重组CD4或抗CD4或gp120的单克隆抗体完全抑制。然而，抗CD4抗体不会诱导单核细胞产生α干扰素。HIV-1诱导的α干扰素产生被抗gp120的V3环决定簇和CD4结合位点的抗体抑制。此外，来自HIV-1感染患者的血清和纯化免疫球蛋白也抑制HIV-1诱导的α干扰素产生。这些观察结果表明，与HIV-1感染患者中α干扰素产生相关的潜在保护性抗病毒反应被抗gp120抗体的产生所抑制。
