A role for NKT cells in the regulation of ongoing type 2 immune responses?

Background: Exogenous IL-12 administration to humans or mice with ongoing immediate hypersensitivity fads to redirect the established allergen-specific type 2 response to one associated with clinical tolerance. Indeed, it markedly exacerbates specific IgE production. Here we investigate the mechanism by which this potent type 1 cytokine promotes type 2 immunity. Methods: C57BL6, BALB/c and CDI-/- mice were OVA immunized, rested 30-180 days, then treated with rIL-12 in an effort to modulate OVA specific recall Ab and cytokine responses. IL-4,S,13, chemokine and antibody responses were determined. Results: rIL-12 administration markedly exacerbated ongoing type 2 immune responses, resulting in 2-5 fold increases in specific IgE and 15-50 fold increases in OVA stimulated IL-4 production. Such exacerbations of type 2 immunity upon IL-12 treatment were abolished in NKT cell deficient CD1-/- mice. Conclusions: Collectively, the data suggest that NKT cells, primarily thought of for their role in innate immunity and influencing induction of adaptive immune responses, may act as important regulators of ongoing immediate hypersensitivity.