title: IL-10-producing NKT10 cells are a distinct regulatory invariant NKT cell subset.
abstract: Invariant natural killer T (iNKT) cells rapidly produce copious amounts of multiple cytokines after activation, thereby impacting a wide variety of different immune reactions. However, strong activation of iNKT cells with α-galactosylceramide (αGalCer) reportedly induces a hyporeactive state that resembles anergy. In contrast, we determined here that iNKT cells from mice pretreated with αGalCer retain cytotoxic activity and maintain the ability to respond to TCR-dependent as well as TCR-independent cytokine-mediated stimulation. Additionally, αGalCer-pretreated iNKT cells acquired characteristics of regulatory cells, including production and secretion of the immunomodulatory cytokine IL-10. Through the production of IL-10, αGalCer-pretreated iNKT cells impaired antitumor responses and reduced disease in experimental autoimmune encephalomyelitis, a mouse model of autoimmune disease. Furthermore, a subset of iNKT cells with a similar inhibitory phenotype and function were present in mice not exposed to αGalCer and were enriched in mouse adipose tissue and detectable in human PBMCs. These data demonstrate that IL-10-producing iNKT cells with regulatory potential (NKT10 cells) represent a distinct iNKT cell subset.
authors: Duygu
authors: D
authors: Sag
authors: Petra
authors: P
authors: Krause
authors: Catherine C
authors: CC
authors: Hedrick
authors: Mitchell
authors: M
authors: Kronenberg
authors: Gerhard
authors: G
authors: Wingender
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control; D005699:Galactosylceramides / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D055611:Natural Killer T-Cells / Q000276:immunology*
chemical_list: D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D016753:Interleukin-10; D007371:Interferon-gamma