Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Department of Immunology, Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.
Microbiol Immunol. 2020 Jun;64(6):458-468. doi: 10.1111/1348-0421.12789. Epub 2020 May 4.
HIV replication can be inhibited by CXCR5 CD8 T cells (follicular cytotoxic T cell [TFC]) which transfer into B-cell follicles where latent HIV infection persists. However, how cytokines affect TFC remain unclear. Understanding which cytokines show the ability to affect TFC could be a key strategy toward curing HIV. Similar mechanisms could be used for the growth and transfer of TFCs and follicular helper T (TFH) cells; as a result, we hypothesized that cytokines IL-6, IL-21, and transforming growth factor-β (TGF-β), which are necessary for the differentiation of TFH cells, could also dictate the development of TFCs. In this work, lymph node mononuclear cells and peripheral blood mononuclear cells from HIV-infected individuals were cocultured with IL-6, IL-21, and TGF-β. We then carried out T-cell receptor (TCR) repertoire analysis to compare the differences between CXCR5 and CXCR5 CD8 T cells. Our results showed that the percentage and function of TFC can be enhanced by stimulation with TGF-β. Besides, TGF-β stimulation enhanced the diversity of TCR and complementarity-determining region 3 sequences. HIV DNA showed a negative correlation with TFC. The use of TGF-β to promote the expression of CXCR5 CD8 T cells could become a new treatment approach for curing HIV.
HIV 的复制可以被 CXCR5 CD8 T 细胞（滤泡细胞毒性 T 细胞[TFC]）抑制，这些细胞转移到潜伏 HIV 感染持续存在的 B 细胞滤泡中。然而，细胞因子如何影响 TFC 尚不清楚。了解哪些细胞因子具有影响 TFC 的能力可能是治愈 HIV 的关键策略。类似的机制可用于 TFC 和滤泡辅助 T（TFH）细胞的生长和转移；因此，我们假设对于 TFH 细胞分化是必需的细胞因子 IL-6、IL-21 和转化生长因子-β（TGF-β）也可以决定 TFC 的发育。在这项工作中，从 HIV 感染个体的淋巴结单核细胞和外周血单核细胞中提取单核细胞和外周血单核细胞，与 IL-6、IL-21 和 TGF-β 共培养。然后，我们进行了 T 细胞受体（TCR）谱分析，以比较 CXCR5 和 CXCR5 CD8 T 细胞之间的差异。结果表明，TGF-β 的刺激可以增强 TFC 的百分比和功能。此外，TGF-β 刺激增强了 TCR 和互补决定区 3 序列的多样性。HIV DNA 与 TFC 呈负相关。使用 TGF-β 促进 CXCR5 CD8 T 细胞的表达可能成为治愈 HIV 的一种新治疗方法。
