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.