Hada Akanksha, Li Lei, Kandel Anmol, Jin Younggeon, Xiao Zhengguo
Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA.
Pathogens. 2023 Sep 19;12(9):1173. doi: 10.3390/pathogens12091173.
Intraepithelial T lymphocytes (T-IELs), which constitute over 50% of the total T lymphocytes in the animal, patrol the mucosal epithelial lining to defend against pathogen invasion while maintaining gut homeostasis. In addition to expressing T cell markers such as CD4 and CD8, T-IELs display T cell receptors (TCR), including either TCRαβ or TCRγδ. Both humans and mice share similar T-IEL subsets: TCRγδ, TCRαβCD8αα, TCRαβCD4, and TCRαβCD8αβ. Among these subsets, human T-IELs are predominantly TCRαβ (over 80%), whereas those in mice are mostly TCRγδ (60%). Of note, the majority of the TCRγδ subset expresses CD8αα in both species. Although T-IELs have been extensively studied in humans and mice, their profiles in cattle have not been well examined. Our study is the first to characterize bovine T-IELs using flow cytometry, where we identified several distinct features. The percentage of TCRγδ was comparable to that of TCRαβ T-IELs (both ~50% of CD3), and the majority of bovine TCRγδ T-IELs did not express CD8 (CD8) (above 60%). Furthermore, about 20% of TCRαβ T-IELs were CD4CD8αβ, and the remaining TCRαβ T-IELs were evenly distributed between CD4 and CD8αβ (40% of TCRαβ T-IELs each) with no TCRαβCD8αα identified. Despite these unique properties, bovine T-IELs, similar to those in humans and mice, expressed a high level of CD69, an activation and tissue-retention marker, and a low level of CD62L, a lymphoid adhesion marker. Moreover, bovine T-IELs produced low levels of inflammatory cytokines such as IFNγ and IL17A, and secreted small amounts of the immune regulatory cytokine TGFβ1. Hence, bovine T-IELs' composition largely differs from that of human and mouse, with the dominance of the CD8 population among TCRγδ T-IELs, the substantial presence of TCRαβCD4CD8αβ cells, and the absence of TCRαβCD8αα T-IELs. These results provide the groundwork for conducting future studies to examine how bovine T-IELs respond to intestinal pathogens and maintain the integrity of the gut epithelial barrier in animals.
上皮内T淋巴细胞（T-IELs）占动物体内总T淋巴细胞的50%以上，它们巡逻于黏膜上皮内层，以抵御病原体入侵，同时维持肠道内环境稳定。除了表达CD4和CD8等T细胞标志物外，T-IELs还展示T细胞受体（TCR），包括TCRαβ或TCRγδ。人类和小鼠拥有相似的T-IEL亚群：TCRγδ、TCRαβCD8αα、TCRαβCD4和TCRαβCD8αβ。在这些亚群中，人类T-IELs主要为TCRαβ（超过80%），而小鼠中的T-IELs大多为TCRγδ（约60%）。值得注意的是，在这两个物种中，大多数TCRγδ亚群都表达CD8αα。尽管T-IELs在人类和小鼠中已得到广泛研究，但其在牛体内的情况尚未得到充分研究。我们的研究首次使用流式细胞术对牛T-IELs进行表征，在此过程中我们确定了几个明显特征。TCRγδ的百分比与TCRαβ T-IELs相当（均约占CD3的50%），并且大多数牛TCRγδ T-IELs不表达CD8（CD8）（超过60%）。此外，约20%的TCRαβ T-IELs为CD4CD8αβ，其余的TCRαβ T-IELs在CD4和CD8αβ之间均匀分布（各约占TCRαβ T-IELs的40%），未发现TCRαβCD8αα。尽管具有这些独特特性，但与人类和小鼠中的T-IELs相似，牛T-IELs表达高水平的CD69（一种激活和组织保留标志物）和低水平的CD62L（一种淋巴细胞粘附标志物）。此外，牛T-IELs产生低水平的炎性细胞因子，如IFNγ和IL17A，并分泌少量免疫调节细胞因子TGFβ1。因此，牛T-IELs的组成与人类和小鼠的有很大不同，TCRγδ T-IELs中CD8群体占主导，存在大量TCRαβCD4CD8αβ细胞，且不存在TCRαβCD8αα T-IELs。这些结果为今后研究牛T-IELs如何应对肠道病原体以及维持动物肠道上皮屏障的完整性奠定了基础。
