Blood Research Institute, Versiti Wisconsin, Milwaukee, WI 53226, USA.
Blood Research Institute, Versiti Wisconsin, Milwaukee, WI 53226, USA; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Immunity. 2022 Mar 8;55(3):475-493.e5. doi: 10.1016/j.immuni.2022.01.018. Epub 2022 Feb 24.
CD4 T cell-derived interleukin 21 (IL-21) sustains CD8 T cell responses during chronic viral infection, but the helper subset that confers this protection remains unclear. Here, we applied scRNA and ATAC-seq approaches to determine the heterogeneity of IL-21CD4 T cells during LCMV clone 13 infection. CD4 T cells were comprised of three transcriptionally and epigenetically distinct populations: Cxcr6 Th1 cells, Cxcr5 Tfh cells, and a previously unrecognized Slamf6 memory-like (Tml) subset. T cell differentiation was specifically redirected toward the Tml subset during chronic, but not acute, LCMV infection. Although this subset displayed an enhanced capacity to accumulate and some developmental plasticity, it remained largely quiescent, which may hinder its helper potential. Conversely, mixed bone marrow chimera experiments revealed that Tfh cell-derived IL-21 was critical to sustain CD8 T cell responses and viral control. Thus, strategies that bolster IL-21Tfh cell responses may prove effective in enhancing CD8 T cell-mediated immunity.
CD4 T 细胞衍生的白细胞介素 21（IL-21）在慢性病毒感染期间维持 CD8 T 细胞反应，但赋予这种保护作用的辅助亚群仍不清楚。在这里，我们应用 scRNA 和 ATAC-seq 方法来确定 LCMV 克隆 13 感染期间 IL-21CD4 T 细胞的异质性。CD4 T 细胞由三种转录和表观遗传上不同的群体组成：Cxcr6 Th1 细胞、Cxcr5 Tfh 细胞和以前未被识别的 Slamf6 记忆样（Tml）亚群。在慢性而非急性 LCMV 感染期间，T 细胞分化专门向 Tml 亚群重新定向。尽管这个亚群表现出增强的积累能力和一些发育可塑性，但它仍然基本处于静止状态，这可能会阻碍其辅助作用。相反，混合骨髓嵌合体实验表明，Tfh 细胞衍生的 IL-21 对于维持 CD8 T 细胞反应和病毒控制至关重要。因此，增强 IL-21Tfh 细胞反应的策略可能在增强 CD8 T 细胞介导的免疫方面证明是有效的。
