title: Suppressor function of liver mononuclear cells isolated during murine chronic graft-vs-host disease. II. Role of prostaglandins and interferon-gamma.
abstract: Mononuclear inflammatory cells (MC) isolated from the livers and spleens of mice with chronic graft-vs-host disease (CGVHD) to minor histocompatibility antigens (B10.D2----BALB/c) show defective proliferation when stimulated with Con A and LPS. In turn, both CGVHD liver and spleen cells suppress the proliferation of mitogen-stimulated normal spleen cells in a genetically unrestricted manner. The suppressor activity of CGVHD spleen cells is mediated by plastic nonadherent null (natural suppressor) cells and involves a soluble suppressor factor(s). In contrast, the suppressor activity of CGVHD liver cells is mediated by macrophages (M phi). In the current studies we show that the suppressor activity of CGVHD liver cells is also mediated by soluble factors and compare the roles of prostaglandins and interferon (IFN)-gamma in mediating defective proliferation and suppressor activities of CGVHD liver and spleen MC. Monoclonal antibody to IFN-gamma partially reversed the defective mitogen-stimulated proliferation of CGVHD spleen MC but had no effect on proliferative response of CGVHD liver MC. Indomethacin did not alter the low proliferative response of either CGVHD liver or spleen MC. Anti-IFN-gamma inhibited the ability of CGVHD spleen cells to suppress proliferation of Con A and LPS-stimulated B10.D2 spleen cells. In contrast, anti-IFN-gamma resulted in a small decrease in the ability of liver MC to suppress Con A (but not LPS)-stimulated cell proliferation. Indomethacin decreased the ability of both CGVHD liver and spleen cells to suppress Con A-stimulated proliferation but had inconsistent effects on LPS-stimulated proliferation. These results show that IFN-gamma and prostaglandins partially mediate the suppressor activity of CGVHD spleen MC. The suppressor activity of CGVHD liver MC also involves prostaglandins but is relatively independent of IFN-gamma.
authors.affiliation: University of Colorado School of Medicine, Denver.
authors.forename: C D
authors.initials: CD
authors.lastname: Howell
authors.forename: T Y
authors.initials: TY
authors.lastname: Yoder
authors.forename: J M
authors.initials: JM
authors.lastname: Vierling
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured / Q000187:drug effects; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013491:Suppressor Factors, Immunologic / Q000032:analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000906:Antibodies; D008934:Mitogens; D013491:Suppressor Factors, Immunologic; D007371:Interferon-gamma; D007213:Indomethacin