CD8 T cell clones inhibit antitumor T cell function by secreting IL-10

Abstract

We have reported that in irradiated, long-term surviving RFM strain of mice there is enhanced kinetics of tumor development upon challenge with RFM lymphoma cells. We reported that we cloned splenic oncofetal (OFA)-specific, noncytotoxic CD8+ T cells from such mice. These noncytotoxic CD8+ T cell clones secrete a factor upon Ag stimulation that inhibits the ability of OFA-specific RFM cytotoxic T (TC) cell clones from killing 5T RFM lymphoma cells in vitro. These supernatants do not inhibit the tumor cell-induced proliferation of the TC cell clones however. We report here that OFA-stimulated, RFM-noncytotoxic CD8 T cell clone culture supernatants also inhibit IFN-γ-secretion by stimulated CD4 and CD8 RFM anti-OFA effector T cell clones in a dose-dependent manner. The inhibitor in those culture supernatants acts in neither an Ag-specific nor MHC-restricted manner. We find that the culture supernatants of OFA-stimulated, noncytotoxic CD8 T cell clones contain IL-10, while those from OFA-stimulated, RFM OFA-specific TC cell clones do not. We show that monoclonal anti-IL-10 Ab specifically blocks the inhibition of cytotoxic activity and IFN-γ secretion by OFA-specific CD8 and CD4 effector T cell clones in a dose-dependent manner in vitro. Incorporation of anti-IL-10 Ab into the cytotoxicity assays of the OFA-specific, noncytotoxic CD8+ T cell clones against 5T tumor cells restores their cytotoxic activity. This may suggest that one way of inducing anergic T cells is by induction of IL-10 secretion.