title: IFN-gamma promotes generation of IL-10 secreting CD4+ T cells that suppress generation of CD8 responses in an antigen-experienced host.
abstract: Ags characterizing tumors or chronic viral infection are generally presented to the host immune system before specific immunotherapy is initiated, and consequent generation of regulatory CD4(+) T cells can inhibit induction of desired effector CD8 T cell responses. IL-10 produced in response to ongoing Ag exposure inhibits generation of CD8 T cells in an Ag-experienced host. We now show that this IL-10 is produced by Ag experienced CD4(+) glucocorticoid-induced tumor necrosis factor receptor(+) T cells that also secrete IFN-gamma upon antigenic stimulation, that IL-10 secretion by these cells is enhanced through IFN-gamma signaling, and, unexpectedly, that IFN-gamma signaling is required for inhibition of generation of Ag-specific CD8 T cell responses in an Ag-experienced host. Systemic inhibition of both IL-10 and IFN-gamma at the time of immunization may therefore facilitate induction of effective immunotherapeutic responses against tumor specific and viral Ags.
authors.affiliation: University of Queensland Diamantina Institute for Cancer, Immunology and Metabolic Medicine, Princess Alexandra Hospital, Woolloongabba, Brisbane, Australia.
authors.forename: Xiao Song
authors.initials: XS
authors.lastname: Liu
authors.forename: Joanne
authors.initials: J
authors.lastname: Leerberg
authors.forename: Kelli
authors.initials: K
authors.lastname: MacDonald
authors.forename: Graham R
authors.initials: GR
authors.lastname: Leggatt
authors.forename: Ian H
authors.initials: IH
authors.lastname: Frazer
mesh_terms: D000818:Animals; D052688:Bovine papillomavirus 1 / Q000276:immunology; D015704:CD4 Antigens / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D036022:Capsid Proteins / Q000008:administration & dosage / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005260:Female; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000378:metabolism / Q000502:physiology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000502:physiology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism* / Q000821:virology
chemical_list: D015704:CD4 Antigens; D036022:Capsid Proteins; D053645:Interleukin-2 Receptor alpha Subunit; D018124:Receptors, Tumor Necrosis Factor; D016753:Interleukin-10; D007371:Interferon-gamma