Inhibition of T Helper Cell Type 2 Cell Differentiation and Immunoglobulin E Response by Ligand-activated V14 Natural Killer T Cells

Correspondence to: Toshinori Nakayama, Department of Molecular Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. Tel:81-43-226-2200 Fax:81-43-227-1498 E-mail:nakayama{at}med.m.chiba-u.ac.jp.

Murine V14 natural killer T (NKT) cells are thought to play a crucial role in various immune responses, including infectious, allergic, and autoimmune diseases. Because V14 NKT cells produce large amounts of both interleukin (IL)-4 and interferon (IFN)- upon in vivo stimulation with a specific ligand, -galactosylceramide (-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 V14 NKT cells that play a dominant role on the Th cell differentiation still remains controversial. Here, we demonstrate by using V14 NKT-deficient mice that V14 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 -GalCer, V14 NKT cells are found to suppress antigen-specific IgE production. The suppression appeared to be IgE specific, and was not detected in either V14 NKT– or IFN-–deficient mice. Consistent with these results, we also found that ligand-activated V14 NKT cells inhibited Th2 cell differentiation in an in vitro induction culture system. Thus, it is likely that activated V14 NKT cells exert a potent inhibitory effect on Th2 cell differentiation and subsequent IgE production by producing a large amount of IFN-. In marked contrast, our studies have revealed that IL-4 produced by V14 NKT cells has only a minor effect on Th2 cell differentiation.

Key Words: interferon , interleukin 4, Nippostrongylus brasiliensis, ovalbumin, suppression

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