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 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.
Grohmann
U
U
Department of Experimental Medicine, University of Perugia, Italy.
Bianchi
R
R
Belladonna
M L
ML
Silla
S
S
Fallarino
F
F
Fioretti
M C
MC
Puccetti
P
P
D000276:Adjuvants, Immunologic / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism*; D016827:CD8 Antigens / Q000096:biosynthesis*; D002469:Cell Separation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D004357:Drug Synergism; D004790:Enzyme Induction / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D009980:Influenza A virus / Q000276:immunology; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000494:pharmacology*; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D016328:NF-kappa B / Q000378:metabolism; D009698:Nucleoproteins / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D010455:Peptides / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D014366:Tryptophan Oxygenase / Q000096:biosynthesis; D014758:Viral Core Proteins / Q000276:immunology
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D016827:CD8 Antigens; D007166:Immunosuppressive Agents; D016328:NF-kappa B; D009698:Nucleoproteins; D010446:Peptide Fragments; D010455:Peptides; D014758:Viral Core Proteins; C122116:nucleoprotein (147-155); D018664:Interleukin-12; D007371:Interferon-gamma; D014366:Tryptophan Oxygenase