FcγRIII discriminates between 2 subsets of Vγ9Vδ2 effector cells with different responses and activation pathways

Upon recognition of nonpeptidic phosphoantigens, human Vδ2 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 Vδ2 population, 2 distinct and complementary subsets with regard to phenotype, mode of activation, and type of responses can be identified: Vδ2 TEMh 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 γ (IFN-γ) and tumor necrosis factor α (TNF-α) in response to T-cell receptor (TCR)–specific stimulation by phosphoantigens; and Vδ2TEMRA cells, which constitutively express several NKRs, high amounts of perforin, but low levels of chemokine receptors and of IFN-γ. These NK-like cells are refractory to phosphoantigen but respond to activation via FcγRIII (CD16) and are highly active against tumoral target cells. Thus, circulating Vδ2T lymphocytes comprise 2 functionally diverse subsets of effector memory cells that may be discriminated on the basis of CD16 expression.