The extrathymic T-cell differentiation in the murine gut

The gut epithelial border is in continuous contact with exogenous antigens and harbors a distinctive and very abundant CD8 alpha alpha intraepithelial T-lymphocyte effector population. We describe here the characteristics of these cells that distinguish them from all other T-cell types in the body as well as their functions in local protection. We also describe how these cells differentiate from local precursors present in the gut cryptopatches (CPs) following a pathway of T-cell differentiation unique to the gut wall. Finally, we describe the origin of the precursors of CD8 alpha alpha T cells, which come from the bone marrow in athymic mice but are first imprinted in the thymus in euthymic mice. Indeed, CD3(-)CD4(-)CD8(-) T-cell-committed precursors can leave the thymus before T-cell receptor rearrangements and then colonize the gut CPs, proceeding with their differentiation within the gut wall.