U. Grohmann et al., IFN-gamma inhibits presentation of a tumor/self peptide by CD8 alpha(-) dendritic cells via potentiation of the CD8 alpha(+) subset, J IMMUNOL, 165(3), 2000, pp. 1357-1363
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.