The Role of α-Galactosylceramide-Activated Vα14 Natural Killer T Cells in the Regulation of Th2 Cell Differentiation

Abstract

Vα14 natural killer T (NKT) cells produce large amounts of both IL-4 and IFN-γ upon stimulation with a ligand, α-galactosylceramide (α-GalCer), and play a crucial role in various immune responses, including allergic diseases. Interestingly, Vα14 NKT cells are not essential for the induction of IgE responses but rather induce suppression of specific IgE production upon activation. The suppression in the IgE production is not detected either in Vα14 NKT cell-deficient mice or in IFN-γ-deficient mice. Thus, activated Vα14 NKT cells are likely to exert a potent suppressive activity on Th2 cell differentiation and subsequent IgE production by producing a large amount of IFN-γ. In marked contrast, little regulatory effect of IL-4 produced by Vα14 NKT cells on Th2 cell differentiation is suggested.

The Interleukin-4 Enhancer CNS-2 Is Regulated by Notch Signals and Controls Initial Expression in NKT Cells and Memory-Type CD4 T Cells

“…NKT and MP cells are thought to be possible alternate sources of IL-4; however, a role for NKT is controversial since a-galcer-activated NKT cells predominantly promote Th1 responses (Cui et al, 1999;Nakayama et al, 2001), while NKT cells are also essential for antigen-induced Th2-mediated airway and IgE response (Akbari et al, 2003;Lisbonne et al, 2003;Yoshimoto et al, 2003;Yoshimoto and Paul, 1994). On the other hand, the CNS-2 active MP subset develops even in OVA-specific TCR Tg mice, and the deletion of this subset impaired antigen-induced Th2 development.…”