The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/9/783/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 6, September 20, 1999 783-792


Original Article

Inhibition of T Helper Cell Type 2 Cell Differentiation and Immunoglobulin E Response by Ligand-Activated V{alpha}14 Natural Killer T Cells

Junqing Cuia, Naohiro Watanabec, Tetsu Kawanoa, Masakatsu Yamashitab, Tohru Kamataa, Chiori Shimizua, Motoko Kimuraa, Eiko Shimizua, Jyunzo Koikea, Haruhiko Kosekia, Yujiro Tanakab, Masaru Taniguchia, and Toshinori Nakayamaa

a CREST (Core Research for Evolution Science and Technology) Project, Japan Science and Technology Corporation, Department of Molecular Immunology, Graduate School of Medicine, Chiba University,
b Department of Developmental Immunology, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
c Department of Tropical Medicine, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105, Japan
Department of Molecular Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.81-43-227-149881-43-226-2200

nakayama{at}med.m.chiba-u.ac.jp

Murine V{alpha}14 natural killer T (NKT) cells are thought to play a crucial role in various immune responses, including infectious, allergic, and autoimmune diseases. Because V{alpha}14 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 V{alpha}14 NKT cells that play a dominant role on the Th cell differentiation still remains controversial. Here, we demonstrate by using V{alpha}14 NKT-deficient mice that V{alpha}14 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, V{alpha}14 NKT cells are found to suppress antigen-specific IgE production. The suppression appeared to be IgE specific, and was not detected in either V{alpha}14 NKT– or IFN-{gamma}–deficient mice. Consistent with these results, we also found that ligand-activated V{alpha}14 NKT cells inhibited Th2 cell differentiation in an in vitro induction culture system. Thus, it is likely that activated V{alpha}14 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 V{alpha}14 NKT cells has only a minor effect on Th2 cell differentiation.

Key Words: interferon {gamma} • interleukin 4 • Nippostrongylus brasiliensis • ovalbumin • suppression


1used in this paper: {alpha}-GalCer, {alpha}-galactosylceramide; B6, C57BL/6; Nb, Nippostrongylus brasiliensis; NKT cells, natural killer T cells; NKT-KO mice, V{alpha}14 NKT-deficient mice; PCA, passive cutaneous anaphylaxis; RAG–/–, recombination-activating gene 1–deficient; RT, reverse transcriptase; V{alpha}14 NKT mice, RAG–/– V{alpha}14Tg Vβ8.2Tg mice

© 1999 The Rockefeller University Press


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