IFN-γ 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-γ upon antigenic stimulation, that IL-10 secretion by these cells is enhanced through IFN-γ signaling, and, unexpectedly, that IFN-γ 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-γ at the time of immunization may therefore facilitate induction of effective immunotherapeutic responses against tumor specific and viral Ags.