Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Center for Immunology and Inflammatory Diseases and Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Sci Immunol. 2022 Jul;7(73):eabc5500. doi: 10.1126/sciimmunol.abc5500. Epub 2022 Jul 1.
T helper 17 (T17) cells located at the Peyer's patch (PP) inductive site and at the lamina propria effector site of the intestinal immune system are responsive to both pathogenic and commensal bacteria. Their plasticity to convert into follicular helper T (T) cells has been proposed to be central to gut immunoglobulin A (IgA) responses. Here, we used an IL-17A fate reporter mouse and an MHC-II tetramer to analyze antigen-specific CD4 T cell subsets and isolate them for single-cell RNA sequencing after oral immunization with cholera toxin and ovalbumin. We found a T-dominated response with only rare antigen-specific T17 cells (<8%) in the PP. A clonotypic analysis provided little support that clonotypes were shared between T and T17 cells, arguing against T17 plasticity as a major contributor to T differentiation. Two mouse models of T17 deficiency confirmed that gut IgA responses to oral immunization do not require T17 cells, with mice exhibiting normal germinal centers in PP and unperturbed total IgA production in the intestine.
辅助性 T 细胞 17（T17）细胞位于派尔集合淋巴结（PP）的诱导部位和肠道免疫系统的固有层效应部位，对病原性和共生细菌均有反应。它们向滤泡辅助性 T（Tfh）细胞转化的可塑性被认为是肠道免疫球蛋白 A（IgA）反应的核心。在这里，我们使用 IL-17A 命运报告小鼠和 MHC-II 四聚体，在口服霍乱毒素和卵清蛋白免疫后，分析抗原特异性 CD4 T 细胞亚群并对其进行单细胞 RNA 测序。我们发现，在 PP 中 T 细胞主导的反应仅存在极少数（<8%）抗原特异性 T17 细胞。克隆型分析几乎没有支持 T 和 T17 细胞之间共享克隆型，这表明 T17 细胞的可塑性不是 T 细胞分化的主要贡献者。两种 T17 缺陷的小鼠模型证实，口服免疫后的肠道 IgA 反应不需要 T17 细胞，与对照相比， 小鼠的 PP 中出现正常的生发中心，肠道中的总 IgA 产生也未受到干扰。
