Functional development of γδ T cells

The thymus generates T cells that are generally functionally immature and thus require peripheral activation for differentiation into effector lymphocytes. Notable exceptions to this rule are murine γδ T cells, many of which have been shown to acquire their functional potential during thymic development from late embryonic stages. Here, we review the underlying ontogenic processes and molecular differentiation mechanisms of murine γδ T cells, focusing on the transcriptional control of IFN-γ and IL-17 expression. We propose that functional commitment of γδ T cells occurs in "developmental windows" defined by the molecular composition of the thymic microenvironment, such as T-cell receptor (TCR), TCR coreceptor ligands, and cytokines. We further discuss the similarities and particularities of functional development of γδ T cells in mice and humans, while highlighting some key unresolved issues for future investigation.