Germ-line and rearranged Tcrd transcription distinguish bona fide NK cells and NK-like γδ T cells

NK cells and γδ T cells are distinct subsets of lymphocytes that contextually share multiple phenotypic and functional characteristics. However, the acquisition and the extent of these similarities remain poorly understood. Here, using T cell receptor δ locus-histone 2B-enhanced GFP (Tcrd-H2BEGFP) reporter mice, we show that germ-line transcription of Tcrd occurs in all maturing NK cells. We also describe a population of mouse NK-like cells that are indistinguishable from “bona fide” NK cells using standard protocols. Requirements for V(D)J recombination and a functional thymus, along with very low-level expression of surface TCRγδ but high intracellular CD3, define these cells as γδ T cells. “NK-like γδ T cells” are CD127+, have a memory-activated phenotype, express multiple NK cell receptors and readily produce interferon-γ in response to IL-12/IL-18 stimulation. The close phenotypic resemblance between NK cells and NK-like γδ T cells is a source of experimental ambiguity in studies bridging NK and T cell biology, such as those on thymic NK cell development. Instead, it ascribes chronic TCRγδ engagement as a means of acquiring NK-like function. See accompanying commentary: at http://dx.doi.org/10.1002/eji.200737418