Inhibitory killer cell immunoglobulin-like receptors strengthen CD8(+) T cell-mediated control of HIV-1, HCV, and HTLV-1.

Inhibitory killer cell immunoglobulin-like receptors strengthen CD8(+) T cell-mediated control of HIV-1, HCV, and HTLV-1.
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DOI:
10.1126/sciimmunol.aao2892
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发表时间:
2018-11-09
期刊:
影响因子:
24.8
通讯作者:
Asquith B
Asquith B
中科院分区:
医学1区
文献类型:
--
作者:
Boelen L;Debebe B;Silveira M;Salam A;Makinde J;Roberts CH;Wang ECY;Frater J;Gilmour J;Twigger K;Ladell K;Miners KL;Jayaraman J;Traherne JA;Price DA;Qi Y;Martin MP;Macallan DC;Thio CL;Astemborski J;Kirk G;Donfield SM;Buchbinder S;Khakoo SI;Goedert JJ;Trowsdale J;Carrington M;Kollnberger S;Asquith B

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杀伤细胞免疫球蛋白样受体(KIR)主要在自然杀伤细胞上表达,在调节先天免疫应答中发挥关键作用。最近的研究表明,抑制性KIR也可以影响适应性T细胞介导的免疫。在小鼠和体外人T细胞中,抑制性KIR连接增强了CD 8 + T细胞存活。为了研究这些观察结果的临床相关性,我们对HIV-1、丙型肝炎病毒(HCV)和人类T细胞白血病病毒(HTLV-1)感染个体的多个独立队列进行了广泛的免疫遗传学分析,并结合T细胞存活的体外测定、体外KIR表达分析和宿主病毒动力学的数学建模。我们的数据表明,抑制性KIR的功能参与增强了CD 8 + T细胞对HIV-1,HCV和HTLV-1的应答,并且是所有三种病毒感染的临床结果的重要决定因素。
Killer-cell immunoglobulin-like receptors (KIRs) are expressed predominantly on natural killer cells, where they play a key role in the regulation of innate immune responses. Recent studies show that inhibitory KIRs can also impact adaptive T cell-mediated immunity. In mice and in human T cells in vitro, inhibitory KIR ligation enhanced CD8+ T cell survival. To investigate the clinical relevance of these observations, we conducted an extensive immunogenetic analysis of multiple, independent cohorts of HIV-1, hepatitis C virus (HCV) and human T cell leukemia virus (HTLV-1)-infected individuals in conjunction with in vitro assays of T cell survival, analysis of ex vivo KIR expression and mathematical modeling of host-virus dynamics. Our data suggest that functional engagement of inhibitory KIRs enhances the CD8+ T cell response against HIV-1, HCV and HTLV-1 and is a significant determinant of clinical outcome in all three viral infections.
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