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.

Yoshimoto T, Min B, Sugimoto T, Hayashi N, Ishikawa Y, Sasaki Y, Hata H, Takeda K, Okumura K, Van Kaer L, Paul WE, Nakanishi K
J Exp Med. 2003 197 (8): 997-1005

PMID: 12695491 · PMCID: PMC2193873 · DOI:10.1084/jem.20021701

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.

MeSH Terms (24)

Animals Antigens, CD1 Antigens, CD1d B-Lymphocytes CD4-Positive T-Lymphocytes CD40 Ligand Cells, Cultured Female Immunoglobulin E Interleukin-2 Interleukin-4 Interleukin-9 Interleukin-13 Interleukin-18 Interleukin-18 Receptor alpha Subunit Killer Cells, Natural Lymphocyte Activation Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Receptors, Interleukin Receptors, Interleukin-18 Th2 Cells

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