Destined for the intestine: thymic selection of TCRαβ CD8αα intestinal intraepithelial lymphocytes

The immune system is composed of a variety of different T-cell lineages distributed through both secondary lymphoid tissue and non-lymphoid tissue. The intestinal epithelium is a critical barrier surface that contains numerous intraepithelial lymphocytes that aid in maintaining homeostasis at that barrier. This review focuses on T-cell receptor alpha beta (TCR alpha beta) CD8 alpha alpha intraepithelial lymphocytes, and how recent advances in the field clarify how this unique T-cell subset is selected, matures, and functions in the intestines. We consider how the available evidence reveals a story of ontogeny starting from agonist selection of T cells in the thymus and finishing through the specific signaling environment of the intestinal epithelium. We conclude with how this story raises further key questions about the development of different ontogenic waves of TCR alpha beta CD8 alpha alpha IEL and their importance for intestinal epithelial homeostasis.

Automated summary

The immune system consists of various T-cell lineages distributed in both lymphoid and non-lymphoid tissues. The intestinal epithelium contains intraepithelial lymphocytes that play a crucial role in maintaining barrier homeostasis. This review focuses on T-cell receptor alpha beta (TCR alpha beta) CD8 alpha alpha intraepithelial lymphocytes, discussing their development and functions in the intestines. The available evidence suggests an ontogenic story starting from agonist selection of T cells in the thymus and ending with the specific signaling environment of the intestinal epithelium. The development of different waves of TCR alpha beta CD8 alpha alpha intraepithelial lymphocytes and their importance for intestinal epithelial homeostasis raise further key questions.