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Original Article |
14 Natural Killer T Cells
nakayama{at}med.m.chiba-u.ac.jp
Murine V
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
14 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 V
14 NKT cells that play a dominant role on the Th cell differentiation still remains controversial. Here, we demonstrate by using V
14 NKT-deficient mice that V
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
-GalCer, V
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
14 NKT– or IFN-
–deficient mice. Consistent with these results, we also found that ligand-activated V
14 NKT cells inhibited Th2 cell differentiation in an in vitro induction culture system. Thus, it is likely that activated V
14 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 V
14 NKT cells has only a minor effect on Th2 cell differentiation.
Key Words: interferon
interleukin 4 Nippostrongylus brasiliensis ovalbumin suppression
-GalCer,
-galactosylceramide; B6, C57BL/6; Nb, Nippostrongylus brasiliensis; NKT cells, natural killer T cells; NKT-KO mice, V
14 NKT-deficient mice; PCA, passive cutaneous anaphylaxis; RAG–/–, recombination-activating gene 1–deficient; RT, reverse transcriptase; V
14 NKT mice, RAG–/– V
14Tg Vβ8.2Tg mice © 1999 The Rockefeller University Press
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