Dendritic cell-derived IL-12 is not required for the generation of cytotoxic, IFN-gamma-secreting, CD8(+) CTL in vivo

By using adoptive transfer of Ag-loaded bone marrow-derived dendritic cells (BMDC), we have established an in vivo model of CTL priming. Activation of CTL in these experiments required both CD4(+) T cells and CD154, demonstra ting that this model reflects CD4(+) T cell-dependent dendritic cell (DC) l icensing. Because IL-12 has been suggested to play an important role in CTL activation by DC, we examined the ability of BMDC to prime CTL in the comp lete absence of IL-12 using p40-deficient mice. We observed that the absenc e of IL-12 does not affect the phenotype or allostimulatory function of BMD C after in vitro maturation. Moreover, there was no difference in the abili ty of Ag-loaded DC to elicit CTL cytotoxicity, whether the Ag was delivered by virus infection or peptide pulsing. Equal frequencies of Ag-specific, I FN-gamma -secreting CD8(+) T cells developed in both wild-type and IL-12-de ficient backgrounds. Finally, CTL generated in the IL-12-deficient environm ent were capable of protecting immunized mice against tumor challenge, demo nstrating that these CTL were fully functional, despite the absence of IL-1 2 during the maturation process in vivo. These results indicate that IL-12 is not critical for the development of IFN-gamma secreting, CD8(+) T cells and that another mechanism must be used by licensed DC to prime and activat e CTL.