CD8 follicular T cells localize throughout the follicle during germinal center reactions and maintain cytolytic and helper properties.

CD8 follicular T cells localize throughout the follicle during germinal center reactions and maintain cytolytic and helper properties.
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CD8滤泡T细胞在生发中心反应期间遍布整个滤泡,并维持细胞溶解和辅助特性。

DOI:
10.1016/j.jaut.2021.102690
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发表时间:
2021-09
影响因子:
12.8
通讯作者:
Hoyer, Katrina K.
Hoyer, Katrina K.
中科院分区:
医学1区
文献类型:
--
作者:
Valentine, Kristen M.;Mullins, Genevieve N.;Davalos, Oscar A.;Seow, Lek Wei;Hoyer, Katrina K.

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滤泡CXCR 5 + PD-1+ CD 8 T细胞(CD 8 Tfc)出现在多种系统性自身免疫模型中,但其对疾病的功能贡献仍存在争议。在这里,我们定义的滤泡定位和功能的相互作用的CD 8 Tfc与B细胞在自身免疫性疾病。自身免疫中功能性T调节细胞的缺乏允许CD 8 Tfc的发育,然后随着淋巴细胞增生而扩大。在全身性自身免疫期间,CD 8 Tfc在淋巴结和脾脏内可被识别,但在组织限制性自身免疫疾病期间则不可识别。自身免疫CD 8 Tfc细胞是多功能的,产生辅助细胞因子IL-21、IL-4和IFNγ,同时维持溶细胞蛋白CD 107 a、颗粒酶B和TNF。在自身免疫性疾病期间,IL-2-KO CD 8 T细胞浸润B细胞滤泡和生发中心,包括暗区,并通过IL-4分泌在体外诱导幼稚B细胞中活化诱导的胞苷脱氨酶。CD 8 Tfc代表了一种独特的CD 8 T细胞群,具有多种效应细胞因子库,可促进致病性自身免疫B细胞应答。
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.
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