Although γ:δ T cells arise from the same progenitors as α:β T cells, most mature γ:δ T cells are components of the innate rather than the adaptive immune system. When their maturation in the thymus is complete, the cells have acquired a defined effector function that can be rapidly elicited following their activation. After emigration from the thymus, most γ:δT cells home to mucosal and epithelial sites in the body, and take up stable residence in these locations.
In mice, the majority of γ:δ T cells in the body arise during embryonic development and the early neonatal period. In the fetal thymus, the first T cells to develop are γ:δ T cells that all express T-cell receptors assembled from the same Vγ and Vδ regions (Fig 8.22). These cells populate the epidermis; the T cells become wedged among the keratinocytes and adopt a dendritic-like form that has given them the name of dendritic epidermal T cells (dETCs) (Fig. 8.23). DETCs provide surveillance of the skin and respond to infection and injury by producing cytokines and chemokines. These factors induce inflammation to enhance pathogen clearance, and they promote wound healing to repair lesions in the skin. In steady-state conditions, dETCs also produce growth factors that help maintain epidermal growth and survival.
Following the dETC cells, a second subset of γ:δ T cells develops in the fetal thymus. These cells home to mucosal epithelia of tissues such as the reproductive tract and the lung, and also to the dermis of the skin. This subset is programmed to produce inflammatory cytokines such as IL-17 when stimulated, and is thought to play a role in responses to infection and injury. Like the dETCs, these IL-17-producing γ:δ T (Tγ:δ-17) cells express T-cell receptors that are essentially invariant, being composed of a single Vγ–Vδ combination. However, the two subsets, dETCs and the fetal Tγ:δ-17 cells, express T-cell receptors that use distinct Vγ gene segments—Vγ5 in the dETCs and Vγ6 in the Tγ:δ-17 cells. As fetal thymocytes do not express the enzyme TdT, there are no N-nucleotides contributing additional diversity at the junctions between V, D, and J gene segments of the T-cell receptors in these two fetally derived