title: Tumor growth changes responsiveness to and production of granulocyte-macrophage colony-stimulating factor during recognition of self MHC class II molecules.
abstract: Tumor growth decreases T-cell recognition of self major histocompatibility complex (MHC) class II molecules by inducing changes in splenic macrophage (M phi) phenotype and function. The current investigation shows tumor-induced alterations in autorecognition also are associated with changes in responsiveness to and production of granulocyte-M phi colony-stimulating factor (GM-CSF). In contrast to normal host (NH) M phi, tumor-bearing host (TBH) M phi failed to express higher MHC class II molecule density after exposure to GM-CSF. Autoreactive T cells stimulated by either NH or TBH M phi were suppressed by GM-CSF. Inhibition of prostaglandin E2 (PGE2) synthesis reversed M-CSF-induced suppression of autoreactivity to NH M phi and, to a lesser extent, to TBH M phi. When TBH autoreactive T cells were stimulated by TBH M phi, autoreactivity increased when GM-CSF was added and PGE2 synthesis was inhibited. Although GM-CSF can contribute to tumor-induced suppression, it did not affect the contribution of GM-CSF during autorecognition. Increased GM-CSF production was responsible, at least in part, for the TBH M phi-mediated suppression. Low concentrations of GM-CSF were produced endogenously by tumor isolates, and GM-CSF production was significantly increased when isolates were stimulated with lipopolysaccharide. Autoreactive T cells stimulated solely by TBH M phi produced more GM-CSF than autoreactive T cells stimulated by NH M phi. Cultures supplemented with several concentrations of NH or TBH M phi produced similar amounts of GM-CSF in a dose-dependent manner. Inhibition of PGE2 synthesis by NH and TBH M phi reduced GM-CSF production equally. Collectively, these results suggest that during tumor growth, responsiveness to and production of GM-CSF alters recognition of self MHC class II molecules.
authors.affiliation: Department of Biology, Virginia Polytechnic Institute and State University, Blacksburg 24061-0406.
authors.forename: T M
authors.initials: TM
authors.lastname: Walker
authors.forename: C J
authors.initials: CJ
authors.lastname: Burger
authors.forename: K D
authors.initials: KD
authors.lastname: Elgert
mesh_terms: D000818:Animals; D015232:Dinoprostone / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012513:Sarcoma, Experimental / Q000276:immunology*
chemical_list: D000949:Histocompatibility Antigens Class II; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015232:Dinoprostone