Selective Conditions Are Required for the Induction of Invariant NKT Cell Hyporesponsiveness by Antigenic Stimulation

Activation of invariant ( i )NKT cells with the model Ag α-galactosylceramide induces rapid production of multiple cytokines, impacting a wide variety of different immune reactions. In contrast, following secondary activation with α-galactosylceramide, the behavior of i NKT cells is altered for months, with the production of most cytokines being strongly reduced. The requirements for the induction of this hyporesponsive state, however, remain poorly defined. In this study, we show that Th1-biasing i NKT cell Ags could induce i NKT cell hyporesponsiveness, as long as a minimum antigenic affinity was reached. In contrast, the Th2-biasing Ag OCH did not induce a hyporesponsive state, nor did cytokine-driven i NKT cell activation by LPS or infections. Furthermore, although dendritic cells and B cells have been reported to be essential for i NKT cell stimulation, neither dendritic cells nor B cells were required to induce i NKT cell hyporesponsiveness. Therefore, our data indicate that whereas some bone marrow–derived cells could induce i NKT cell hyporesponsiveness, selective conditions, dependent on the structure and potency of the Ag, were required to induce hyporesponsiveness.