Tumor Growth Alters Macrophage Responsiveness to Macrophage Colony-Stimulating Factor During Reactivity Against Allogeneic and Syngeneic Mhc Class II Molecules

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Abstract
Tumor-induced changes in macrophage (Mϕ)2 accessory activities significantly suppress T-cell recognition of allogeneic and syngeneic major histocompatibility complex (MHC) class II molecules. Because these changes are often associated with altered responses to stimulatory and inhibitory cytokines, we investigated the possibility that tumor growth alters the contribution of a macrophage regulatory cytokine, macrophage colony-stimulating factor (M-CSF), during reactivity against allogeneic and syngeneic MHC class II molecules. T-cell reactivity against allogeneic MHC class II molecules was significantly suppressed by tumor-bearing host (TBH) Mϕ in the presence of M-CSF. M-CSF-induced suppression was independent of TBH Mϕ prostaglandin E2 (PGE2) synthesis. T-cell reactivity against syngeneic MHC class II molecules increased in the presence of M-CSF when normal host (NH) Mϕ served as the source of syngeneic molecules. However, T-cell reactivity against syngeneic MHC class II molecules in the presence of M-CSF did not change when TBH Mϕ served as stimulator/accessory cells. Although T-cell reactivity against NH syngeneic MHC class II molecules was additively increased by M-CSF and indomethacin (a PGE2 synthesis inhibitor) treatment, reactivity against TBH syngeneic MHC class II molecules increased solely through PGE2 synthesis inhibition. Admixtures of both NH and TBH Mϕ in the absence or presence of M-CSF suggest that tumor-induced suppression was not strictly due to decreased expression of MHC class II molecules. Collectively, these data suggest that TBH Mϕ are partly suppressive through altered responsiveness to M-CSF.