NK cytotoxicity against CD4+ T cells during HIV-1 infection: a gp41 peptide induces the expression of an NKp44 ligand.
NK cytotoxicity against CD4+ T cells during HIV-1 infection: a gp41 peptide induces the expression of an NKp44 ligand.
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HIV-1 感染期间 NK 对 CD4 T 细胞的细胞毒性：gp41 肽诱导 NKp44 配体的表达。
DOI：
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发表时间：
2005
影响因子：
11.1
通讯作者：
P. Debré
中科院分区：
文献类型：
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作者：
V. Vieillard;J. Strominger;P. Debré
HIV感染导致慢性免疫激活状态和免疫功能的进行性恶化，最明显的表现是CD 4 + T细胞的进行性耗竭。来自HIV感染患者的自然杀伤（NK）细胞的相当大百分比被激活并表达天然细胞毒性受体（NCR）NKp 44。在这里，我们表明NKp 44（NKp 44 L）的细胞配体在HIV-1感染期间表达，并与CD 4 + T细胞耗竭的进展和病毒载量的增加相关。表达该配体的CD 4 + T细胞对NKp 44 + NK细胞介导的NK裂解活性高度敏感。NKp 44 L的表达由HIV-1包膜gp 41蛋白的线性基序NH 2-SWSNKS-COOH诱导。这种高度保守的基序似乎对HIV感染患者的CD 4 + T细胞的NK溶解的急剧增加至关重要。这些研究强烈表明，NKp 44 L的诱导在HIV感染中活化的NK细胞裂解CD 4 + T细胞中起关键作用，因此为考虑HIV-1如何使用NK细胞免疫监视来触发CD 4 + T细胞提供了一个框架。了解这一机制可能有助于开发未来的治疗策略和疫苗对抗HIV-1感染。
HIV infection leads to a state of chronic immune activation and progressive deterioration in immune function, manifested most recognizably by the progressive depletion of CD4+ T cells. A substantial percentage of natural killer (NK) cells from patients with HIV infection are activated and express the natural cytotoxicity receptor (NCR) NKp44. Here we show that a cellular ligand for NKp44 (NKp44L) is expressed during HIV-1 infection and is correlated with both the progression of CD4+ T cell depletion and the increase of viral load. CD4+ T cells expressing this ligand are highly sensitive to the NK lysis activity mediated by NKp44+ NK cells. The expression of NKp44L is induced by the linear motif NH2-SWSNKS-COOH of the HIV-1 envelope gp41 protein. This highly conserved motif appears critical to the sharp increase in NK lysis of CD4+ T cells from HIV-infected patients. These studies strongly suggest that induction of NKp44L plays a key role in the lysis of CD4+ T cells by activated NK cells in HIV infection and consequently provide a framework for considering how HIV-1 may use NK cell immune surveillance to trigger CD4+ T cells. Understanding this mechanism may help to develop future therapeutic strategies and vaccines against HIV-1 infection.