TUMOR-GROWTH ALTERS MACROPHAGE RESPONSIVENESS TO MACROPHAGE-COLONY-STIMULATING FACTOR DURING REACTIVITY AGAINST ALLOGENEIC AND SYNGENEIC MHC CLASS-II MOLECULES

Tumor-induced changes in macrophage (Mphi)2 accessory activities signi ficantly suppress T-cell recognition of allogeneic and syngeneic major histocompatibility complex (MHC) class 11 molecules. Because these ch anges are often associated with altered responses to stimulatory and i nhibitory cytokines, we investigated the possibility that tumor growth alters the contribution of a macrophage regulatory cytokine, macropha ge colony-stimulating factor (M-CSF), during reactivity against alloge neic and syngeneic MHC class II molecules. T-cell reactivity against a llogeneic MHC class II molecules was significantly suppressed by tumor -bearing host (TBH) Mphi in the presence of M-CSF. M-CSF-induced suppr ession was independent of TBH Mphi prostaglandin E2 (PGE2) synthesis. T-cell reactivity against syngeneic MHC class II molecules increased i n the presence of M-CSF when normal host (NH) Mphi served as the sourc e of syngeneic molecules. However, T-cell reactivity against syngeneic MHC class II molecules in the presence of M-CSF did not change when T BH Mphi served as stimulator/accessory cells. Although T-cell reactivi ty against NH syngeneic MHC class II molecules was additively increase d by M-CSF and indomethacin (a PGE2 synthesis inhibitor) treatment, re activity against TBH syngeneic MHC class II molecules increased solely through PGE2 synthesis inhibition. Admixtures of both NH and TBH Mphi in the absence or presence of M-CSF suggest that tumor-induced suppre ssion was not strictly due to decreased expression of MHC class II mol ecules. Collectively, these data suggest that TBH Mphi are partly supp ressive through altered responsiveness to M-CSF.