Follicular CXCR5+ PD-1+ CD8 T cells (CD8 Tfc) arise in multiple models of systemic autoimmunity yet their functional contribution to disease remains in debate. Here we define the follicular localization and functional interactions of CD8 Tfc with B cells during autoimmune disease. The absence of functional T regulatory cells in autoimmunity allows for CD8 Tfc development that then expands with lymphoproliferation. CD8 Tfc are identifiable within the lymph nodes and spleen during systemic autoimmunity, but not during tissue-restricted autoimmune disease. Autoimmune CD8 Tfc cells are polyfunctional, producing helper cytokines IL-21, IL-4, and IFNγ while maintaining cytolytic proteins CD107a, granzyme B, and TNF. During autoimmune disease, IL-2-KO CD8 T cells infiltrate the B cell follicle and germinal center, including the dark zone, and in vitro induce activation-induced cytidine deaminase in naïve B cells via IL-4 secretion. CD8 Tfc represent a unique CD8 T cell population with a diverse effector cytokine repertoire that can contribute to pathogenic autoimmune B cell response.

滤泡 CXCR5+ PD-1+ CD8 T 细胞 (CD8 Tfc) 出现在多种系统性自身免疫模型中，但它们对疾病的功能贡献仍存在争议。在这里，我们定义了自身免疫性疾病期间 CD8 Tfc 与 B 细胞的滤泡定位和功能相互作用。自身免疫中缺乏功能性 T 调节细胞允许 CD8 Tfc 发展，然后随着淋巴增殖而扩大。CD8 Tfc 在全身性自身免疫病期间可在淋巴结和脾脏内识别，但在组织限制性自身免疫病期间不能识别。自身免疫性 CD8 Tfc 细胞是多功能的，可产生辅助细胞因子 IL-21、IL-4 和 IFNγ，同时维持溶细胞蛋白 CD107a、颗粒酶 B 和 TNF。在自身免疫性疾病期间，IL-2-KO CD8 T 细胞浸润 B 细胞滤泡和生发中心，包括暗区，并在体外通过 IL-4 分泌在幼稚 B 细胞中诱导活化诱导的胞苷脱氨酶。CD8 Tfc 代表一个独特的 CD8 T 细胞群，具有多种效应细胞因子库，可促成致病性自身免疫 B 细胞反应。