INVITRO INFECTION OF NATURAL-KILLER-CELLS WITH DIFFERENT HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ISOLATES
INVITRO INFECTION OF NATURAL-KILLER-CELLS WITH DIFFERENT HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ISOLATES
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DOI：
10.1128/jvi.65.4.1812-1822.1991
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发表时间：
1991-04-01
影响因子：
5.4
通讯作者：
STARR, SE
中科院分区：
文献类型：
--
作者：
CHEHIMI, J;BANDYOPADHYAY, S;STARR, SE
自然杀伤 (NK) 细胞是白细胞的一个独立子集，与 T 和 B 淋巴细胞不同。 NK 细胞介导对多种靶细胞的自发非 MHC 限制性杀伤，无需事先致敏，并且似乎参与针对某些病毒感染的初始保护。 NK 细胞介导的细胞毒性抑制是艾滋病患者中观察到的众多免疫缺陷之一，可能会导致继发性病毒感染。在这里，我们报告说，既不表达表面 CD4 也不表达 CD4 mRNA 的 NK 细胞的克隆和纯化多克隆群体，很容易受到人类免疫缺陷病毒 1 型 (HIV-1) 的各种分离株的感染。通过检测细胞内和培养上清液中的 p24 抗原、感染细胞内 HIV DNA 的存在以及源自 HIV 感染的 NK 细胞的上清液感染外周血单核细胞或 CD4+ 细胞系的能力，证明病毒复制。抗 CD4 或抗 Fc-gamma-RIII 单克隆抗体不能阻断 NK 细胞的感染。来自 HIV 感染和未感染培养物的 NK 细胞裂解三种不同靶细胞的能力相似。在感染 HIV 的 NK 细胞培养物中，大量细胞死亡。这些结果表明，艾滋病患者中 NK 细胞的丧失是 HIV 感染的直接影响，但 NK 细胞功能的降低涉及另一种机制。必须考虑 NK 细胞作为 HIV-1 潜在储存库的可能性。
Natural killer (NK) cells are a discrete subset of leukocytes, distinct from T and B lymphocytes. NK cells mediate spontaneous non-MHC-restricted killing of a wide variety of target cells without prior sensitization and appear to be involved in initial protection against certain viral infections. Depressed NK cell-mediated cytotoxicity, one of the many immunological defects observed in AIDS patients, may contribute to secondary virus infections. Here we report that clonal and purified polyclonal populations of NK cells, which expressed neither surface CD4 nor CD4 mRNA, were susceptible to infection with various isolates of human immunodeficiency virus type 1 (HIV-1). Viral replication was demonstrated by detection of p24 antigen intracellularly and in culture supernatants, by the presence of HIV DNA within infected cells, and by the ability of supernatants derived from HIV-infected NK cells to infect peripheral blood mononuclear cells or CD4+ cell lines. Infection of NK cells was not blocked by anti-CD4 or anti-Fc-gamma-RIII monoclonal antibodies. NK cells from HIV-infected and uninfected cultures were similar in their ability to lyse three different target cells. Considerable numbers of cells died in HIV-infected NK cell cultures. These results suggest that loss of NK cells in AIDS patients is a direct effect of HIV infection but that reduced NK cell function involves another mechanism. The possibility that NK cells serve as a potential reservoir for HIV-1 must be considered.