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Inhibition of T helper cell type 2 cell differentiation and immunoglobulin E response by ligand-activated Valpha14 natural killer T cells.
Cui J; Watanabe N; Kawano T; Yamashita M; Kamata T; Shimizu C; Kimura M;
December 30, 1999
J Exp Med. 1999 Sep 20;190(6):783-92. Unique Identifier : AIDSLINE

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.

JOURNAL ARTICLE Animal Cell Communication/*IMMUNOLOGY Cell Differentiation/IMMUNOLOGY IgE/BIOSYNTHESIS/*IMMUNOLOGY Immunoglobulin Variable Region/IMMUNOLOGY Interferon Type II/IMMUNOLOGY Interleukin-4/IMMUNOLOGY Killer Cells, Natural/*IMMUNOLOGY Ligands Lymphocyte Transformation/*IMMUNOLOGY Mice Signal Transduction/IMMUNOLOGY Support, Non-U.S. Gov't Th2 Cells/*IMMUNOLOGY