title: Splenic macrophages from tumor-bearing mice co-expressing MAC-1 and MAC-2 antigens exert immunoregulatory functions via two distinct mechanisms.
abstract: Tumor burden has been shown to induce a variety of phenotypic and functional changes in the cellular constituents of the host's immune system. These changes have been implicated as mechanisms by which tumors avoid rejection. Studies of BALB/c mice bearing a D1-DMBA-3 mammary adenocarcinoma showed alterations of the splenocyte populations. There was a five-fold increase of macrophages (M phi) that were phenotypically and functionally analyzed to establish their role in tumor-induced modifications of the host's immune response. Monoclonal antibody staining defined a Mac-1+2+ population which comprised up to 20% of the splenocytes in tumor-bearers (TB), but is negligible in spleens from normal mice. These Mac-1+2+ M phi were found to mediate down-regulation of both polyclonal and antigen-specific T and B cell responses in vitro and in vivo. Although B cell responses were suppressed via prostaglandin E2 (PGE2) production by the TB M phi, T cell responses were relatively refractory to PGE2-mediated down-regulation. Instead, they were suppressed by a contact-dependent T cell-M phi interaction. Furthermore, tumor-derived factors such as granulocyte-M phi colony-stimulating factor (GM-CSF) seem to play an important role in the induction and expansion of the Mac-1+2+ M phi. These cells appear to mediate down-regulation of the host immune responses by at least two distinct mechanisms: 1) PGE2 production and 2) a cell contact-dependent, but non-major-histocompatibility-complex-specific, interaction.
authors.affiliation: Department of Microbiology and Immunology, University of Miami School of Medicine, Florida 33101.
authors.forename: G A
authors.initials: GA
authors.lastname: Watson
authors.forename: Y X
authors.initials: YX
authors.lastname: Fu
authors.forename: D M
authors.initials: DM
authors.lastname: Lopez
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology*; D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis*; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D005434:Flow Cytometry; D037502:Galectin 3; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006867:Hydrolases / Q000032:analysis; D008213:Lymphocyte Activation / Q000187:drug effects; D016177:Macrophage-1 Antigen / Q000032:analysis*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D008325:Mammary Neoplasms, Experimental / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D013154:Spleen / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000943:Antigens, Differentiation; D037502:Galectin 3; D016177:Macrophage-1 Antigen; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006867:Hydrolases; D015232:Dinoprostone