Cutting edge: Gammadelta intraepithelial lymphocytes of the small intestine are not biased toward thymic antigens.

gammadelta Tau cells, together with alphabeta Tau cells, are abundantly present in the epithelial layer of the small intestine (IEL) and are essential for the host's first line of defense. Whether or not gammadelta IELs, like alphabeta IELs, are derived from thymocytes that encounter self-Ags in the thymus is unclear. In this study, we report that a natural population of gammadelta T cells that are specific for the nonclassical MHC class I molecules T10 and T22 are present in the IEL compartment of mice that do not express T10/T22. Furthermore, the small intestinal homing receptor CCR9 is preferentially expressed on gammadelta thymocytes that have yet to encounter a ligand, and gammadelta thymocytes with high affinity for self-ligand are CCR9(low). These observations suggest that the Ag-specific repertoire of gammadelta IELs is not biased toward thymic Ags. Instead, gammadelta IELs appear suited to respond to novel Ags revealed in pathological settings.