Inhibition of T helper cell type 2 cell differentiation and immunoglobulinE response by ligand-activated V alpha 14 natural killer T cells

Murine V alpha 14 natural killer T (NKT) cells are thought to play a crucia l role in various immune responses, including infectious, allergic, and aut oimmune diseases. Because V alpha 14 NKT cells produce large amounts of bot h interleukin (IL)-4 and interferon (IFN)-gamma upon in vivo stimulation wi th a specific ligand, alpha-galactosylceramide (alpha-GalCer), or after tre atment with anti-CD3 antibody, a regulatory role on helper T (Th) cell diff erentiation 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 dispen sable for the induction of antigen-specific immunoglobulin (Ig)E responses induced by ovalbumin immunization or Nipostrongylus brasiliensis infection. However, upon in vivo activation with alpha-GalCer, V alpha 14 NKT cells a re found to suppress antigen-specific IgE production. The suppression appea red to be IgE specific, and was not detected in either V alpha 14 NKT- or I FN-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 differentia tion 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 alp ha 14 NKT cells has only a minor effect on Th2 cell differentiation.