Cutting Edge: γδ Intraepithelial Lymphocytes of the Small Intestine Are Not Biased toward Thymic Antigens

gamma delta T cells, together with alpha beta T 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 gamma delta IELs, like alpha beta IELs, are derived from thymocytes that encounter self-Ags in the thymus is unclear. In this study, we report that a natural population of gamma delta T cells that are specific for the nonclassical MHC class I molecules T 10 and T22 a-re present in the IEL compartment of mice that do not express T10/T22. Furthermore, the small intestinal homing receptor CCR9 is preferentially expressed on gamma delta thymocytes that have yet to encounter a ligand, and gamma delta thymocytes with high affinity for self-ligand are CCR9(low). These observations suggest that the Ag-specific repertoire of gamma delta IELs is not biased toward thymic Ags. Instead, gamma delta IELs appear suited to respond to novel Ags revealed in pathological settings. The Journal of Immunology, 2009, 182: 7348-7351.