Intraepithelial T lymphocytes (T-IEL) contain subsets of innate-like T cells that evoke innate and adaptive immune responses to provide rapid protection at epithelial barrier sites. In the intestine, T-IEL express variable T cell antigen receptors (TCR), with unknown antigen specificities. Intriguingly, they also express multiple inhibitory receptors, many of which are normally found on exhausted or antigen-experienced T cells. This pattern suggests that T-IEL are antigen-experienced, yet it is not clear where, and in what context, T-IEL encounter TCR ligands. We review recent evidence indicating TCR antigens for intestinal innate-like T-IEL are found on thymic or intestinal epithelium, driving agonist selection of T-IEL. We explore the contributions of the TCR and various co-stimulatory and co-inhibitory receptors in activating T-IEL effector functions. The balance between inhibitory and activating signals may be key to keeping these highly cytotoxic, rapidly activated cells in check, and key to harnessing their immune surveillance potential.

中文翻译：

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先天样上皮内 T 淋巴细胞的激活机制。

上皮内 T 淋巴细胞 (T-IEL) 包含先天样 T 细胞亚群，可激发先天和适应性免疫反应，在上皮屏障部位提供快速保护。在肠道中，T-IEL 表达具有未知抗原特异性的可变 T 细胞抗原受体 (TCR)。有趣的是，它们还表达多种抑制性受体，其中许多通常存在于耗尽或抗原经验丰富的 T 细胞上。这种模式表明 T-IEL 是有抗原经验的，但尚不清楚 T-IEL 在何处以及在何种情况下遇到 TCR 配体。我们回顾了最近的证据，表明在胸腺或肠上皮细胞中发现了肠道先天样 T-IEL 的 TCR 抗原，从而推动了 T-IEL 的激动剂选择。我们探讨了 TCR 和各种共刺激和共抑制受体在激活 T-IEL 效应器功能中的作用。抑制信号和激活信号之间的平衡可能是控制这些高细胞毒性、快速激活细胞的关键，也是利用其免疫监视潜力的关键。