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.