Search

NK cells and gammadelta 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 delta 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 TCRgammadelta but high intracellular CD3, define these cells as gammadelta T cells. "NK-like gammadelta T cells" are CD127+, have a memory-activated phenotype, express multiple NK cell receptors and readily produce interferon-gamma in response to IL-12/IL-18 stimulation. The close phenotypic resemblance between NK cells and NK-like gammadelta 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 TCRgammadelta engagement as a means of acquiring NK-like function.

The homeostatic maturation of NK cells is severely impaired in mice lacking the transcription factor T-bet, and the expression of the NK cell maturation marker killer cell lectin-like receptor G1 (KLRG1) has been shown to be dependent on MHC class I molecules. Interferon (IFN)-gamma signaling via the signal transducer and activator of transcription (STAT)1 is vital for T-bet and MHC class I induction. Here we investigated the relationship between STAT1, T-bet, and MHC class I molecules with regard to the phenotypic maturation of peripheral NK cells. We demonstrate that, to varying degrees, the maturation status of peripheral NK cells is impaired in naive mice with deficiencies in STAT1, T-bet, or MHC class I molecules. We find that in naive animals, the expression of wild-type levels of MHC class I molecules in trans is sufficient to restore the maturation profiles of STAT1(-/-) NK cells in vivo. In contrast, expression of T-bet is required in cis for normal NK cell maturation to occur. Additionally, we demonstrate that the activation-induced maturation of NK cells during the course of murine cytomegalovirus (MCMV) infection does not require expression of MHC class I molecules or STAT1 but is severely delayed in the absence of T-bet.