title: Nonredundant roles for CD1d-restricted natural killer T cells and conventional CD4+ T cells in the induction of immunoglobulin E antibodies in response to interleukin 18 treatment of mice.
abstract: Interleukin (IL)-18 synergizes with IL-12 to promote T helper cell (Th)1 responses. Somewhat paradoxically, IL-18 administration alone strongly induces immunoglobulin (Ig)E production and allergic inflammation, indicating a role for IL-18 in the generation of Th2 responses. The ability of IL-18 to induce IgE is dependent on CD4+ T cells, IL-4, and signal transducer and activator of transcription (stat)6. Here, we show that IL-18 fails to induce IgE both in CD1d-/- mice that lack natural killer T (NKT) cells and in class II-/- mice that lack conventional CD4+ T cells. However, class II-/- mice reconstituted with conventional CD4+ T cells show the capacity to produce IgE in response to IL-18. NKT cells express high levels of IL-18 receptor (R)alpha chain and produce significant amounts of IL-4, IL-9, and IL-13, and induce CD40 ligand expression in response to IL-2 and IL-18 stimulation in vitro. In contrast, conventional CD4+ T cells express low levels of IL-18Ralpha and poorly respond to IL-2 and IL-18. Nevertheless, conventional CD4+ T cells are essential for B cell IgE responses after the administration of IL-18. These findings indicate that NKT cells might be the major source of IL-4 in response to IL-18 administration and that conventional CD4+ T cells demonstrate their helper function in the presence of NKT cells.
authors.affiliation: Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Booki
authors.initials: B
authors.lastname: Min
authors.forename: Takaaki
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Nobuki
authors.initials: N
authors.lastname: Hayashi
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Hitomi
authors.initials: H
authors.lastname: Hata
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Luc
authors.initials: L
authors.lastname: Van Kaer
authors.forename: William E
authors.initials: WE
authors.lastname: Paul
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakanishi
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics / Q000378:metabolism*; D055610:Antigens, CD1d; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000276:immunology*; D018793:Interleukin-13 / Q000378:metabolism; D020382:Interleukin-18 / Q000276:immunology* / Q000378:metabolism; D053727:Interleukin-18 Receptor alpha Subunit; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D016906:Interleukin-9 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D053724:Receptors, Interleukin-18; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; C508573:Il18r1 protein, mouse; D018793:Interleukin-13; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D007376:Interleukin-2; D016906:Interleukin-9; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D023201:CD40 Ligand; D015847:Interleukin-4; D007073:Immunoglobulin E