title: Inhibition of T helper cell type 2 cell differentiation and immunoglobulin E response by ligand-activated Valpha14 natural killer T cells.
abstract: Murine Valpha14 natural killer T (NKT) cells are thought to play a crucial role in various immune responses, including infectious, allergic, and autoimmune diseases. Because Valpha14 NKT cells produce large amounts of both interleukin (IL)-4 and interferon (IFN)-gamma upon in vivo stimulation with a specific ligand, alpha-galactosylceramide (alpha-GalCer), or after treatment with anti-CD3 antibody, a regulatory role on helper T (Th) cell differentiation has been proposed for these cells. However, the identity of the cytokine produced by Valpha14 NKT cells that play a dominant role on the Th cell differentiation still remains controversial. Here, we demonstrate by using Valpha14 NKT-deficient mice that Valpha14 NKT cells are dispensable for the induction of antigen-specific immunoglobulin (Ig)E responses induced by ovalbumin immunization or Nippostrongylus brasiliensis infection. However, upon in vivo activation with alpha-GalCer, Valpha14 NKT cells are found to suppress antigen-specific IgE production. The suppression appeared to be IgE specific, and was not detected in either Valpha14 NKT- or IFN-gamma-deficient mice. Consistent with these results, we also found that ligand-activated Valpha14 NKT cells inhibited Th2 cell differentiation in an in vitro induction culture system. Thus, it is likely that activated Valpha14 NKT cells exert a potent inhibitory effect on Th2 cell differentiation and subsequent IgE production by producing a large amount of IFN-gamma. In marked contrast, our studies have revealed that IL-4 produced by Valpha14 NKT cells has only a minor effect on Th2 cell differentiation.
authors.affiliation: CREST (Core Research for Evolution Science and Technology) Project, Department of Molecular Immunology, Chiba, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Cui
authors.forename: N
authors.initials: N
authors.lastname: Watanabe
authors.forename: T
authors.initials: T
authors.lastname: Kawano
authors.forename: M
authors.initials: M
authors.lastname: Yamashita
authors.forename: T
authors.initials: T
authors.lastname: Kamata
authors.forename: C
authors.initials: C
authors.lastname: Shimizu
authors.forename: M
authors.initials: M
authors.lastname: Kimura
authors.forename: E
authors.initials: E
authors.lastname: Shimizu
authors.forename: J
authors.initials: J
authors.lastname: Koike
authors.forename: H
authors.initials: H
authors.lastname: Koseki
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Taniguchi
authors.forename: T
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D015398:Signal Transduction / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D007135:Immunoglobulin Variable Region; D008024:Ligands; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma