Innate and adaptive γδ T cells: How, when, and why

gamma delta T cells comprise the third cell lineage of lymphocytes that use, like alpha beta T cells and B cells, V(D)J gene rearrangement with the potential to generate a highly diverse T cell receptor (TCR) repertoire. There is no obvious conservation of gamma delta T cell subsets (based on TCR repertoire and/or function) between mice and human, leading to the notion that human and mouse gamma delta T cells are highly different. In this review, we focus on human gamma delta T cells, building on recent studies using high-throughput sequencing to analyze the TCR repertoire in various settings. We make then the comparison with mouse gamma delta T cell subsets highlighting the similarities and differences and describe the remarkable changes during lifespan of innate and adaptive gamma delta T cells. Finally, we propose mechanisms contributing to the generation of innate versus adaptive gamma delta T cells. We conclude that key elements related to the generation of the gamma delta TCR repertoire and gamma delta T cell activation/development are conserved between human and mice, highlighting the similarities between these two species.