Tissue-resident memory T (T_RM) cells provide key adaptive immune responses in infection, cancer, and autoimmunity. However, transcriptional heterogeneity of human intestinal T_RM cells remains undefined. Here, we investigate transcriptional and functional heterogeneity of human T_RM cells through study of donor-derived T_RM cells from intestinal transplant recipients. Single-cell transcriptional profiling identifies two transcriptional states of CD8⁺ T_RM cells, delineated by ITGAE and ITGB2 expression. We define a transcriptional signature discriminating these populations, including differential expression of cytotoxicity- and residency-associated genes. Flow cytometry of recipient-derived cells infiltrating the graft, and lymphocytes from healthy gut, confirm these CD8⁺ T_RM phenotypes. CD8⁺ CD69⁺CD103⁺ T_RM cells produce interleukin-2 (IL-2) and demonstrate greater polyfunctional cytokine production, whereas β2-integrin⁺CD69⁺CD103⁻ T_RM cells have higher granzyme expression. Analysis of intestinal CD4⁺ T cells identifies several parallels, including a β2-integrin⁺ population. Together, these results describe the transcriptional, phenotypic, and functional heterogeneity of human intestinal CD4⁺ and CD8⁺ T_RM cells.

组织驻留记忆 T (T _RM ) 细胞在感染、癌症和自身免疫中提供关键的适应性免疫反应。然而，人类肠道 T _RM细胞的转录异质性仍未确定。在这里，我们通过研究来自肠移植受者的供体来源的 T _{RM细胞来研究人类 T RM}细胞的转录和功能异质性。单细胞转录谱确定了 CD8 ⁺ T _RM细胞的两种转录状态，由ITGAE和ITGB2 描绘表达。我们定义了区分这些群体的转录特征，包括细胞毒性和驻留相关基因的差异表达。浸润移植物的受体衍生细胞和来自健康肠道的淋巴细胞的流式细胞术证实了这些 CD8 ⁺ T _RM表型。CD8 ⁺ CD69 ⁺ CD103 ⁺ T _RM细胞产生白细胞介素-2 (IL-2) 并表现出更多的多功能细胞因子产生，而 β2-整合素⁺ CD69 ⁺ CD103 ^- T _RM细胞具有更高的颗粒酶表达。肠道CD4 ^+分析T 细胞确定了几个相似之处，包括 β2-整合素⁺群体。^{总之，这些结果描述了人类肠道 CD4 +}和 CD8 ⁺ T _RM细胞的转录、表型和功能异质性。