Gut intraepithelial lymphocyte development

CD8alphabeta(+) 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 alpha4beta7-integrin-driven homing all along the gut mucosa. In contrast, CD8alphaalpha(+) intraepithelial lymphocytes, which may be TCRgammadelta(+) or alphabeta(+), 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.