Gamma delta T-cell differentiation and effector function programming, TCR signal strength, when and how much?

• We review work on the signals affecting the commitment of γδ versus αβ lineage T cells.
• We review the interplay between TCR signal strength and E protein activity.
• We review how the acquisition of different γδ T cell effector functions is regulated.
• We examined whether γδ17 cells can be generated from adult hematopoietic progenitors.

γδ T-cells boast an impressive functional repertoire that can paint them as either champions or villains depending on the environmental and immunological cues. Understanding the function of the various effector γδ subsets necessitates tracing the developmental program of these subsets, including the point of lineage bifurcation from αβ T-cells. Here, we review the importance of signals from the T-cell receptor (TCR) in determining αβ versus γδ lineage fate, and further discuss how the molecular components of this pathway may influence the developmental programming of γδ T-cells functional subsets. Additionally, we discuss the role of temporal windows in restricting the development of IL-17 producing γδ T-cell subtypes, and explore whether fetal and adult hematopoietic progenitors maintain the same potential for giving rise to this important subset.