Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States.
Institute of Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, United States.
Elife. 2023 Dec 21;12:RP90466. doi: 10.7554/eLife.90466.
Intestinal intraepithelial lymphocytes (IELs) are characterized by an unusual phenotype and developmental pathway, yet their specific ligands and functions remain largely unknown. Here by analysis of QFL T cells, a population of CD8 T cells critical for monitoring the MHC I antigen processing pathway, we established that unconventional Qa-1-restricted CD8 T cells are abundant in intestinal epithelium. We found that QFL T cells showed a Qa-1-dependent unconventional phenotype in the spleen and small intestine of naïve wild-type mice. The splenic QFL T cells showed innate-like functionality exemplified by rapid response to cytokines or antigens, while the gut population was refractory to stimuli. Microbiota was required for the maintenance, but not the initial gut homing of QFL T cells. Moreover, monocolonization with which expresses a peptide that cross-activated QFL T cells, was sufficient to maintain QFL T cells in the intestine. Thus, microbiota is critical for shaping the Qa-1-restricted IEL landscape.
肠上皮内淋巴细胞（IEL）具有独特的表型和发育途径，但它们的特定配体和功能仍知之甚少。在这里，我们通过对 QFL T 细胞（一种对监测 MHC I 抗原加工途径至关重要的 CD8 T 细胞群体）的分析，确定了非常规的 Qa-1 限制性 CD8 T 细胞在肠道上皮中大量存在。我们发现，QFL T 细胞在 naive 野生型小鼠的脾脏和小肠中表现出依赖于 Qa-1 的非常规表型。脾 QFL T 细胞表现出先天样功能，例如对细胞因子或抗原的快速反应，而肠道群体对刺激无反应。微生物群对于 QFL T 细胞的维持是必需的，但不是其最初在肠道中的归巢所必需的。此外，单定植一种表达可交叉激活 QFL T 细胞的肽的细菌足以维持肠道中的 QFL T 细胞。因此，微生物群对于塑造 Qa-1 限制性 IEL 景观至关重要。
