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

Abstract

γδ Τ cells, together with αβ Τ 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 γδ IELs, like αβ IELs, are derived from thymocytes that encounter self-Ags in the thymus is unclear. In this study, we report that a natural population of γδ 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 γδ thymocytes that have yet to encounter a ligand, and γδ thymocytes with high affinity for self-ligand are CCR9low. These observations suggest that the Ag-specific repertoire of γδ IELs is not biased toward thymic Ags. Instead, γδ IELs appear suited to respond to novel Ags revealed in pathological settings.