Multidimensional single-cell analyses of T cells have fueled the debate about whether there is extensive plasticity or ‘mixed’ priming of helper T cell subsets in vivo. Here, we developed an experimental framework to probe the idea that the site of priming in the systemic immune compartment is a determinant of helper T cell–induced immunopathology in remote organs. By site-specific in vivo labeling of antigen-specific T cells in inguinal (i) or gut draining mesenteric (m) lymph nodes, we show that i-T cells and m-T cells isolated from the inflamed central nervous system (CNS) in a model of multiple sclerosis (MS) are distinct. i-T cells were Cxcr6⁺, and m-T cells expressed P2rx7. Notably, m-T cells infiltrated white matter, while i-T cells were also recruited to gray matter. Therefore, we propose that the definition of helper T cell subsets by their site of priming may guide an advanced understanding of helper T cell biology in health and disease.

T 细胞的多维单细胞分析引发了关于体内辅助性 T 细胞亚群是否存在广泛可塑性或“混合”启动的争论。在这里，我们开发了一个实验框架来探讨系统免疫区室中的启动位点是远程器官中辅助性 T 细胞诱导的免疫病理学的决定因素。通过对腹股沟 (i) 或肠道引流肠系膜 (m) 淋巴结中的抗原特异性 T 细胞进行体内位点特异性标记，我们表明在一个模型中从发炎的中枢神经系统 (CNS) 中分离出 iT 细胞和 mT 细胞多发性硬化症 (MS) 是不同的。iT 细胞是 Cxcr6 ⁺和 mT 细胞表达 P2rx7。值得注意的是，mT 细胞渗透到白质中，而 iT 细胞也被募集到灰质中。因此，我们建议，通过启动位点定义辅助性 T 细胞亚群可能有助于深入了解健康和疾病中的辅助性 T 细胞生物学。