Innate immunity in human immunodeficiency virus infection: Effect of viremia on natural killer cell function

Innate immunity in human immunodeficiency virus infection: Effect of viremia on natural killer cell function
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DOI:
10.1086/368222
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发表时间:
2003-04-01
影响因子:
6.4
通讯作者:
Fauci, AS
Fauci, AS
中科院分区:
医学2区
文献类型:
--
作者:
Kottilil, S;Chun, TW;Fauci, AS

文献摘要

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我们研究了病毒血症对细胞接触和可溶性因子介导的自体自然杀伤(NK)和CD 8(+)T细胞对HIV-1感染者CD 4(+)T细胞中内源性人类免疫缺陷病毒(HIV)复制的抑制作用。NK细胞和CD 8(+)T细胞一样有效地抑制HIV复制。NK细胞培养上清对HIV复制的抑制作用主要由CC-趋化因子分泌介导,并且在无病毒血症患者中的抑制作用显著大于有病毒血症患者。此外,病毒血症水平与NK细胞和NK衍生上清液抑制病毒复制的能力之间呈负相关。NK细胞控制HIV复制的能力与干扰素-γ表达水平和细胞溶解活性无关。我们的研究结果表明,NK介导的HIV复制抑制与CD 8(+)T细胞一样有效;它主要由CC-趋化因子的分泌介导,病毒血症的存在显著削弱了这种NK介导的HIV复制抑制作用。
We examined the effect of viremia on cell contact and soluble factor-mediated suppression of endogenous human immunodeficiency virus (HIV) replication in CD4(+) T cells from HIV-1-infected individuals by autologous natural killer (NK) and CD8(+) T cells. NK cells suppressed HIV replication as effectively as did CD8(+) T cells. Suppression of HIV replication by NK cell culture supernatant was predominantly mediated by CC-chemokine secretion and was considerably greater in patients without viremia than in patients with viremia. Furthermore, there was an inverse correlation between the level of viremia and the ability of NK cells and NK-derived supernatants to suppress virus replication. The ability of NK cells to control HIV replication was independent of levels of interferon-gamma expression and cytolytic activity. Our results demonstrate that NK-mediated suppression of HIV replication is as potent as that of CD8(+) T cells; it is mediated predominantly by secretion of CC-chemokines, and the presence of viremia markedly impairs this NK-mediated inhibitory effect on HIV replication.