Gut intraepithelial lymphocyte development

CD8αβ+ and CD4+ intraepithelial lymphocytes, the progeny of double-positive thymocytes, are oligoclonal T-cell populations that have accumulated in the gut wall as the result of repeated antigenic stimulations, which lead to rounds of traffic through the lymph/blood circuit ending in an α4β7-integrin-driven homing all along the gut mucosa. In contrast, CD8αα+ intraepithelial lymphocytes, which may be TCRγδ+ or αβ+, result in part from local differentiation in the gut, but studies comparing euthymic and athymic mice suggest a thymic double-negative origin for many of them.