IFN-gamma inhibits presentation of a tumor/self peptide by CD8 alpha(-) dendritic cells via potentiation of the CD8 alpha(+) 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 mi nority population of CD8(+) dendritic cells (DC) negatively regulates the i nduction of T cell reactivity by peptide-loaded CD8(-) DC in DBA/2 mice. Ho wever, 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 recipien t hosts. We report here that exposure of CD8(+) DC to IFN-gamma greatly enh ances their inhibitory activity on Ag presentation by the other subset, blo cking the ability of IL-12-treated CD8(-) DC to overcome suppression. In co ntrast, IFN-gamma has no direct effects on the APC function of the latter c ells and does not interfere with IL-12 signaling. The negative regulatory e ffect triggered by IFN-gamma in CD8(+) DC appears to involve interference w ith tryptophan metabolism in vivo. Through tryptophan depletion affecting T cell responses, IFN-gamma acting on CD8(+) DC may thus contribute to regul ation of immunity to tumor/self peptides presented by the CD8(-) subset.