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

Tomohiro Yoshimoto, Booki Min, Takaaki Sugimoto, Nobuki Hayashi, Yuriko Ishikawa, Yuki Sasaki, Hitomi Hata, Kazuyoshi Takeda, Ko Okumura, Luc Van Kaer, William E. Paul, Kenji Nakanishi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

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)α 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-18Rα 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.

Original languageEnglish (US)
Pages (from-to)997-1005
Number of pages9
JournalJournal of Experimental Medicine
Volume197
Issue number8
DOIs
StatePublished - Apr 21 2003
Externally publishedYes

Keywords

  • Allergy
  • CD4 NK1.1 T cells
  • CD40 ligand
  • IL-18R
  • Th2 cytokines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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