Positive selection of dendritic epidermal γδ T cell precursors in the fetal thymus determines expression of skin-homing receptors

The role of cellular selection in the development of gammadelta T cells remains unclear. Knockout mice lacking a subset of Vgamma genes, including Vgamma3, contain abundant gammadelta T cells but are devoid of dendritic epidermal gammadeltaT cells (DETCs), which normally express an invariant Vgamma3/Vdelta1 gammadelta TCR. A rearranged Vgamma2 transgene restored DETC development, but the restored DETCs selectively expressed a unique Vdelta gene other than Vdelta1, indicating that DETC development involves TCR-based selection. In both normal and transgenic/knockout mice, specific DETC precursors in the fetal thymus were activated and expressed the IL-15 receptor beta chain, skin-homing receptors, and thymic exiting receptors. In vitro activation of irrelevant precursors also led to upregulation of the skin-homing receptor, providing an explanation for how thymic selection is coordinated with development of epidermal gammadelta T cells.