IFN-gamma promotes generation of IL-10 secreting CD4+ T cells that suppress generation of CD8 responses in an antigen-experienced host.
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.
Liu
Xiao Song
XS
University of Queensland Diamantina Institute for Cancer, Immunology and Metabolic Medicine, Princess Alexandra Hospital, Woolloongabba, Brisbane, Australia.
Leerberg
Joanne
J
MacDonald
Kelli
K
Leggatt
Graham R
GR
Frazer
Ian H
IH
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
D015704:CD4 Antigens; D036022:Capsid Proteins; D053645:Interleukin-2 Receptor alpha Subunit; D018124:Receptors, Tumor Necrosis Factor; D016753:Interleukin-10; D007371:Interferon-gamma