Hioki Kaito A, Liang Xueting, Lynch Adam C, Ranjan Ravi, Pobezinskaya Elena L, Pobezinsky Leonid A
Molecular and Cellular Biology Program, University of Massachusetts, Amherst, MA, United States.
Department of Veterinary and Animal Science, University of Massachusetts, Amherst, MA, United States.
Front Immunol. 2025 Aug 5;16:1637209. doi: 10.3389/fimmu.2025.1637209. eCollection 2025.
Intestinal intraepithelial lymphocytes (IELs) are a versatile population of immune cells with both effector and regulatory roles in gut immunity. Although this functional diversity is thought to arise from distinct IEL subpopulations, the heterogeneity of TCRαβ and TCRγδ IELs have not been well characterized. Using scRNAseq, we identified CD8αα T cell subsets with memory-like ( ) and effector-like ( ) profiles in both TCRαβ and TCRγδ IELs. Using CD160 and CD122 as markers of memory-like and effector-like cells, respectively, we found that while effector-like cells dominated the small intestine, memory-like IELs were more prevalent in the large intestine, suggesting a functional specialization of immune responses along the gut. Further transcriptional analysis revealed shared profiles between TCRαβ and TCRγδ small intestinal IEL subsets, suggesting conserved functional roles across these populations. Finally, our analysis indicated that TCRαβ memory-like IELs arise from double-negative (DN) precursors, and that effector-like IELs subsequently differentiate from the memory-like population. In contrast, TCRγδ IELs appear to originate from two distinct precursor populations, one expressing and the other , indicating the presence of parallel developmental pathways within this lineage. Overall, our findings reveal that both TCRαβ and TCRγδ cells contain memory-like and effector-like subsets, which may contribute to the functional heterogeneity of IELs.
肠道上皮内淋巴细胞（IELs）是一类多功能的免疫细胞群体，在肠道免疫中兼具效应和调节作用。尽管这种功能多样性被认为源于不同的IEL亚群，但TCRαβ和TCRγδ IELs的异质性尚未得到充分表征。利用单细胞RNA测序（scRNAseq），我们在TCRαβ和TCRγδ IELs中均鉴定出具有记忆样（ ）和效应样（ ）特征的CD8αα T细胞亚群。分别使用CD160和CD122作为记忆样细胞和效应样细胞的标志物，我们发现虽然效应样细胞在小肠中占主导，但记忆样IELs在大肠中更为普遍，这表明肠道免疫反应存在功能特化。进一步的转录分析揭示了TCRαβ和TCRγδ小肠IEL亚群之间的共同特征，表明这些群体具有保守的功能作用。最后，我们的分析表明，TCRαβ记忆样IELs源自双阴性（DN）前体细胞，而效应样IELs随后从记忆样群体中分化而来。相比之下，TCRγδ IELs似乎起源于两个不同的前体群体，一个表达 ，另一个表达 ，这表明该谱系中存在平行的发育途径。总体而言，我们的研究结果表明，TCRαβ和TCRγδ细胞均包含记忆样和效应样亚群，这可能导致IELs的功能异质性。
