FcgammaRIII discriminates between 2 subsets of Vgamma9Vdelta2 effector cells with different responses and activation pathways

Upon recognition of nonpeptidic phosphoantigens, human Vdelta2 T lymphocytes enter a lineage differentiation pattern that determines the generation of memory cells with a range of effector functions. Here, we show that within the effector memory Vdelta2 population, 2 distinct and complementary subsets with regard to phenotype, mode of activation, and type of responses can be identified: Vdelta2 T(EMh) cells, which express high levels of chemokine receptors, but low levels of perforin and of natural killer receptors (NKRs) and which produce large amounts of interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) in response to T-cell receptor (TCR)-specific stimulation by phosphoantigens; and Vdelta2T(EMRA) cells, which constitutively express several NKRs, high amounts of perforin, but low levels of chemokine receptors and of IFN-gamma. These NK-like cells are refractory to phosphoantigen but respond to activation via FcgammaRIII (CD16) and are highly active against tumoral target cells. Thus, circulating Vdelta2T lymphocytes comprise 2 functionally diverse subsets of effector memory cells that may be discriminated on the basis of CD16 expression.