The key sites within the gastrointestinal (GI) tract where T cells mediate effector responses and the impact of these responses on intestinal stem cells (ISCs) remain unclear. Using experimental bone marrow transplantation to model immune-mediated GI damage and 3D imaging to analyze T cell localization, we found that the ISC compartment is the primary intestinal site targeted by T cells after transplantation. Recruitment to the crypt base region resulted in direct T cell engagement with the stem cell compartment and loss of crypt base columnar ISCs, which expressed both MHC classes I and II. Vasculature expressing the adhesion molecule MAdCAM-1 clustered near the crypt base, preferentially regulating crypt compartment invasion and ISC reduction without affecting T cell migration to villi. These findings indicate that allogeneic T cells rapidly access the stem cell niche after transplantation, and this targeted recruitment to the stem cell compartment results in ISC loss during immune-mediated GI damage.

中文翻译：

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异体移植后，肠干细胞隔室的T细胞募集会驱动免疫介导的肠道损伤。

胃肠道（GI）中的T细胞介导效应器反应的关键部位，这些反应对肠干细胞（ISC）的影响仍不清楚。使用实验性骨髓移植对免疫介导的GI损伤进行建模并使用3D成像分析T细胞定位，我们发现ISC隔室是移植后T细胞靶向的主要肠道部位。隐窝基区的招募导致T细胞与干细胞区室直接接触，并失去隐窝基柱状ISC，后者表达了MHC I类和II类。表达粘附分子MAdCAM-1的脉管聚集在隐窝基部附近，优先调节隐窝隔室的侵袭和ISC的减少，而不会影响T细胞向绒毛的迁移。