The gene expression profile of phosphoantigen‐specific human γδ T lymphocytes is a blend of αβ T‐cell and NK‐cell signatures

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Abstract
Global transcriptional technologies have revolutionised the study of lymphoid cell populations, but human γδ 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 TCRVγ+ γδ 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 TCRVγ+ γδ T cells is a hybrid of those from αβ T and NK cells, with more ‘NK‐cell’ genes than αβ T cells have and more ‘T‐cell’ genes than NK cells. The expression profile of TCRVγ+ γδ 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 γδ T cells, whether resting or clonally expanding, clearly distinctive from that of NK/T or peripheral T‐cell lymphomas of the γδ subtype.

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