Diversity in recognition and function of human γδ T cells

As interest increases in harnessing the potential power of tissue-resident cells for human health and disease, gamma delta T cells have been thrust into the limelight due to their prevalence in peripheral tissues, their sentinel-like phenotypes, and their unique antigen recognition capabilities. This review focuses primarily on human gamma delta T cells, highlighting their distinctive characteristics including antigen recognition, function, and development, with an emphasis on where they differ from their alpha beta T cell comparators, as well as from gamma delta T cell populations in the mouse. We review the antigens that have been identified thus far to regulate members of the human V delta 1 population and discuss what players are involved in transducing phosphoantigen-mediated signals to human V gamma 9V delta 2 T cells. We also briefly review distinguishing features of these cells in terms of TCR signaling, use of coreceptor and costimulatory molecules and their development. These cells have great potential to be harnessed in a clinical setting, but caution must be taken to understand their unique capabilities and how they differ from the populations to which they are commonly compared.