Department of Internal Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, United States.
Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States.
Elife. 2021 Feb 3;10:e54792. doi: 10.7554/eLife.54792.
Generation of tolerogenic peripheral regulatory T (pTreg) cells is commonly thought to involve CD103 gut dendritic cells (DCs), yet their role in commensal-reactive pTreg development is unclear. Using two Helicobacterspecific T cell receptor (TCR) transgenic mouse lines, we found that both CD103 and CD103 migratory, but not resident, DCs from the colon-draining mesenteric lymph node presented Helicobacter antigens to T cells ex vivo. Loss of most CD103 migratory DCs in vivo using murine genetic models did not affect the frequency of Helicobacter-specific pTreg cell generation or induce compensatory tolerogenic changes in the remaining CD103 DCs. By contrast, activation in a Th1-promoting niche in vivo blocked Helicobacter-specific pTreg generation. Thus, these data suggest a model where DC-mediated effector T cell differentiation is 'dominant', necessitating that all DC subsets presenting antigen are permissive for pTreg cell induction to maintain gut tolerance.
诱导外周调节性 T 细胞（pTreg）的产生通常被认为涉及 CD103 肠道树突状细胞（DC），但其在共生反应性 pTreg 发育中的作用尚不清楚。使用两种特定于 Helicobacter 的 T 细胞受体（TCR）转基因小鼠系，我们发现来自结肠引流肠系膜淋巴结的 CD103 和 CD103 迁移性而非驻留性 DC 均可在体外将 Helicobacter 抗原呈递给 T 细胞。使用鼠遗传模型体内缺失大多数 CD103 迁移性 DC 不会影响 Helicobacter 特异性 pTreg 细胞生成的频率，也不会诱导剩余 CD103 DC 发生代偿性耐受变化。相比之下，体内在 Th1 促进龛位中的激活阻断了 Helicobacter 特异性 pTreg 的生成。因此，这些数据表明一种模型，其中 DC 介导的效应 T 细胞分化是“主导”的，需要所有呈递抗原的 DC 亚群都允许 pTreg 细胞诱导以维持肠道耐受。
