Interleukin-21-Producing HIV-1-Specific CD8 T Cells Are Preferentially Seen in Elite Controllers
Interleukin-21-Producing HIV-1-Specific CD8 T Cells Are Preferentially Seen in Elite Controllers
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DOI：
10.1128/jvi.01476-10
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发表时间：
2011-03-01
影响因子：
5.4
通讯作者：
Goepfert, Paul A.
中科院分区：
文献类型：
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作者：
Williams, LaTonya D.;Bansal, Anju;Goepfert, Paul A.
人类免疫缺陷病毒1型（HIV-1）发病机制的一个标志是CD4 T细胞的快速损失导致全身性免疫功能障碍，包括CD8 T细胞表型耗竭。了解控制抗病毒T细胞反应的功能质量和保护潜力的必要因素将有助于合理的疫苗设计和改进治疗策略，以对抗持续感染。慢性病毒感染的小鼠模型表明，主要由CD4 T细胞产生的白细胞介素-21 （IL-21）是产生和维持功能正常的CD8 T细胞和病毒遏制所必需的。我们推断，在HIV-1感染期间保留的IL-21的产生可能与增强的CD8 T细胞功能相关，从而改善病毒控制。在这里，我们分析了CD4和CD8 T细胞在体外受重叠HIV-1肽刺激后产生几种细胞因子和IL-21的能力。CD4和CD8 T细胞都能够在HIV-1感染时产生IL-21，后者细胞类型与病毒控制更密切相关。此外，产生il -21的hiv -1特异性CD4 T细胞（与产生其他细胞因子的CD4 T细胞相比）是功能CD8 T细胞的最佳指标。我们的研究结果表明，hiv -1特异性il -21产生CD8 T细胞在初次感染后被诱导，并在精英控制者中富集，这表明这些细胞在维持病毒血症控制中起关键作用。
A hallmark of human immunodeficiency virus type 1 (HIV-1) pathogenesis is the rapid loss of CD4 T cells leading to generalized immune dysfunction, including an exhausted CD8 T cell phenotype. Understanding the necessary factors that govern the functional quality and protective potential of antiviral T cell responses would facilitate rational vaccine design and improve therapeutic strategies to combat persistent infections. Mouse models of chronic viral infection demonstrate that interleukin-21 (IL-21), produced primarily by CD4 T cells, is required for the generation and maintenance of functionally competent CD8 T cells and viral containment. We reasoned that preserved IL-21 production during HIV-1 infection would be associated with enhanced CD8 T cell function, allowing improved viral control. Here we analyzed the ability of CD4 and CD8 T cells to produce several cytokines in addition to IL-21 ex vivo following stimulation with overlapping HIV-1 peptides. Both CD4 and CD8 T cells were able to produce IL-21 in response to HIV-1 infection, with the latter cell type more closely associated with viral control. Furthermore, IL-21-producing HIV-1-specific CD4 T cells (compared to those producing other cytokines) were the best indicator of functional CD8 T cells. Our results demonstrate that HIV-1-specific IL-21-producing CD8 T cells are induced following primary infection and enriched in elite controllers, suggesting a critical role for these cells in the maintenance of viremia control.