Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana, USA.
FASEB J. 2019 Aug;33(8):8905-8912. doi: 10.1096/fj.201802703R. Epub 2019 Apr 29.
C-C chemokine receptor 5 (CCR5) plays an essential role in HIV pathogenesis as the major coreceptor on CD4 T cells used by HIV, yet the function of CCR5 on CD8 T cells is not well understood. Furthermore, the immunologic effects of the CCR5 inhibitor maraviroc (MVC), despite approval for clinical use, have not yet been well evaluated for their potential effects on cytotoxic T-cell responses. In this study, we characterized the development and function of CCR5CD8 T cells in rhesus macaques with or without Simian immunodeficiency virus (SIV) infection. We also investigated the effects of the CCR5 antagonist MVC on functional CCR5CD8 T-cell responses . The data show that CCR5CD8 T cells have an effector memory phenotype and increase with age in systemic and mucosal lymphoid tissues as a heterogeneous population of polyfunctional CD8 T cells. In addition, CCR5 is highly expressed on SIV gag-specific (CM9) CD8 T cells in SIV-infected macaques, yet CCR5CD8 T cells are significantly reduced in mucosal lymphoid tissues with disease progression. Furthermore, MVC treatment reduced activation and cytokine secretion of CD8 T cells a CCR5-independent pathway. These findings suggest that surface CCR5 protein plays an important role in differentiation and activation of CD8 T cells. Although MVC may be helpful in reducing chronic inflammation and activation, it may also inhibit virus-specific CD8 T-cell responses. Thus optimal use of CCR5 antagonists either alone or in combination with other drugs should be defined by further investigation.-Wang, X., Russell-Lodrigue, K. E., Ratterree, M. S., Veazey, R. S., Xu, H. Chemokine receptor CCR5 correlates with functional CD8 T cells in SIV-infected macaques and the potential effects of maraviroc on T-cell activation.
C-C 趋化因子受体 5（CCR5）在 HIV 发病机制中起着至关重要的作用，因为它是 HIV 使用的 CD4 T 细胞的主要辅助受体，但 CCR5 在 CD8 T 细胞上的功能尚不清楚。此外，尽管 CCR5 抑制剂马拉维若（MVC）已获得临床应用批准，但尚未对其对细胞毒性 T 细胞反应的潜在影响进行充分评估。在这项研究中，我们描述了有无猴免疫缺陷病毒（SIV）感染的恒河猴中 CCR5CD8 T 细胞的发育和功能。我们还研究了 CCR5 拮抗剂 MVC 对功能性 CCR5CD8 T 细胞反应的影响。研究数据表明，CCR5CD8 T 细胞具有效应记忆表型，并随着年龄的增长在全身和黏膜淋巴组织中作为一群异质性的多功能 CD8 T 细胞而增加。此外，在 SIV 感染的猕猴中，CCR5 高度表达于 SIV gag 特异性（CM9）CD8 T 细胞上，但随着疾病的进展，黏膜淋巴组织中的 CCR5CD8 T 细胞明显减少。此外，MVC 治疗可降低 CD8 T 细胞的激活和细胞因子分泌，这是一种 CCR5 非依赖性途径。这些发现表明，表面 CCR5 蛋白在 CD8 T 细胞的分化和激活中起着重要作用。尽管 MVC 可能有助于减少慢性炎症和激活，但它也可能抑制病毒特异性 CD8 T 细胞反应。因此，需要进一步研究来确定 CCR5 拮抗剂单独或与其他药物联合使用的最佳方案。
