IFN-γ inhibits presentation of a tumor/self peptide by CD8α- dendritic cells via potentiation of the CD8α+ subset

Using an in vivo model of tumor/self peptide presentation for induction of class I-restricted skin test reactivity, we have previously shown that a minority population of CD8(+) dendritic cells (DC) negatively regulates the induction of T cell reactivity by peptide-loaded CD8(-) DC in DBA/2 mice. However, the CD8(-) fraction can be primed by IL-12 to overcome inhibition by the CD8(+) subset when the two types of DC are cotransferred into recipient hosts. We report here that exposure of CD8(+) DC to IFN-gamma greatly enhances their inhibitory activity on Ag presentation by the other subset, blocking the ability of IL-12-treated CD8(-) DC to overcome suppression. In contrast, IFN-gamma has no direct effects on the APC function of the latter cells and does not interfere with IL-12 signaling. The negative regulatory effect triggered by IFN-gamma in CD8(+) DC appears to involve interference with tryptophan metabolism in vivo. Through tryptophan depletion affecting T cell responses, IFN-gamma acting on CD8(+) DC may thus contribute to regulation of immunity to tumor/self peptides presented by the CD8(-) subset.