高亲和力 CD4 T 细胞产生的白细胞介素 21 驱动持续性病毒感染期间脑驻留 CD8 T 细胞的分化。
IL-21 from high-affinity CD4 T cells drives differentiation of brain-resident CD8 T cells during persistent viral infection.
机构信息
Department of Microbiology and Immunology, Penn State College of Medicine, Hershey, PA 17033, USA.
Division of Microbiology and Immunology, Department of Pathology, University of Utah, Salt Lake City, UT 84112, USA.
出版信息
Sci Immunol. 2020 Sep 18;5(51). doi: 10.1126/sciimmunol.abb5590.
Development of tissue-resident memory (T) CD8 T cells depends on CD4 T cells. In polyomavirus central nervous system infection, brain CXCR5 PD-1 CD4 T cells produce interleukin-21 (IL-21), and CD8 T cells lacking IL-21 receptors (IL21R) fail to become bT IL-21 CD4 T cells exhibit elevated T cell receptor (TCR) affinity and higher TCR density. IL21R brain CD8 T cells do not express CD103, depend on vascular CD8 T cells for maintenance, are antigen recall defective, and lack T core signature genes. CD4 T cell-deficient and IL21R brain CD8 T cells show similar deficiencies in expression of genes for oxidative metabolism, and intrathecal delivery of IL-21 to CD4 T cell-depleted mice restores expression of electron transport genes in CD8 T cells to wild-type levels. Thus, high-affinity CXCR5 PD-1 CD4 T cells in the brain produce IL-21, which drives CD8 bT differentiation in response to a persistent viral infection.
组织驻留记忆 (T) CD8 T 细胞的发育依赖于 CD4 T 细胞。在多瘤病毒中枢神经系统感染中，脑 CXCR5 PD-1 CD4 T 细胞产生白细胞介素-21 (IL-21)，而缺乏 IL-21 受体 (IL21R) 的 CD8 T 细胞无法成为 bT IL-21 CD4 T 细胞表现出更高的 T 细胞受体 (TCR) 亲和力和更高的 TCR 密度。IL21R 脑 CD8 T 细胞不表达 CD103，依赖血管 CD8 T 细胞维持，抗原回忆缺陷，缺乏 T 核心特征基因。CD4 T 细胞缺陷和 IL21R 脑 CD8 T 细胞在氧化代谢基因表达方面表现出相似的缺陷，向 CD4 T 细胞耗竭的小鼠鞘内给予 IL-21 可将 CD8 T 细胞中电子传递基因的表达恢复至野生型水平。因此，脑内高亲和力 CXCR5 PD-1 CD4 T 细胞产生 IL-21，从而驱动 CD8 bT 分化以应对持续的病毒感染。
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