title: Direct effects of T-bet and MHC class I expression, but not STAT1, on peripheral NK cell maturation.
abstract: 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.
authors.affiliation: Department of Molecular Microbiology and Immunology and Graduate Program in Pathobiology, Division of Biology and Medicine, Brown University, Providence, USA.
authors.forename: Scott H
authors.initials: SH
authors.lastname: Robbins
authors.forename: Marlowe S
authors.initials: MS
authors.lastname: Tessmer
authors.forename: Luc
authors.initials: L
authors.lastname: Van Kaer
authors.forename: Laurent
authors.initials: L
authors.lastname: Brossay
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000276:immunology; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology* / Q000821:virology; D037181:Lectins, C-Type; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000276:immunology; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology; D050794:STAT1 Transcription Factor; D020825:T-Box Domain Proteins; D015534:Trans-Activators / Q000096:biosynthesis* / Q000172:deficiency / Q000276:immunology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000172:deficiency / Q000276:immunology; D000098815:T-bet Transcription Factor
chemical_list: D004268:DNA-Binding Proteins; D015395:Histocompatibility Antigens Class I; C451496:Klrg1 protein, mouse; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors