The gene expression profile of phosphoantigen-specific human ?d T lymphocytes is a blend of aß T-cell and NK-cell signatures

Global transcriptional technologies have revolutionised the study of lymphoid cell populations, but human gamma delta T lymphocytes specific for phosphoantigens remain far less deeply characterised by these methods despite the great therapeutic potential of these cells. Here we analyse the transcriptome of circulating TCRV gamma(+) gamma delta T cells isolated from healthy individuals, and their relation with those from other lymphoid cell subsets. We report that the gene signature of phosphoantigen-specific TCRV gamma(+) gamma delta T cells is a hybrid of those from a beta T and NK cells, with more NK-cell genes than a beta T cells have and more T-cell genes than NK cells. The expression profile of TCRV gamma(+) gamma delta T cells stimulated with phosphoantigen recapitulates their immediate physiological functions: Th1 cytokine, chemokine and cytotoxic activities reflect their high mitotic activity at later time points and do not indicate antigen-presenting functions. Finally, such hallmarks make the transcriptome of gamma delta T cells, whether resting or clonally expanding, clearly distinctive from that of NK/T or peripheral T-cell lymphomas of the gamma delta subtype.