title: Synergistic effect of IFN-gamma and TNF-alpha on expression of immune molecules and antigen presentation by Schwann cells.
abstract: Neonatal rat Schwann cells were characterized with regard to their immune functions in vitro. Without stimulation they displayed low levels of ICAM-1, but not of MHC class II gene products on their surface. Expression of both immune molecules was upregulated by IFN-gamma. TNF-alpha acted synergistically, but had no effect when given alone. ICAM-1 expression reached its maximum within 24 hr, whereas I-A plateaued only after 3 days of cytokine treatment. Increased expression of recognition molecules on Schwann cells correlated well with enhanced activation of CD4+ autoimmune T cell lines between Day 1 and 2. T cell activation was blocked by adding monoclonal antibodies directed against I-A molecules, whereas ICAM-1-specific antibodies exerted a mild costimulatory effect. We conclude that Schwann cells may exert potent immunoregulatory functions by expressing MHC and adhesion molecules, which may be further upregulated by Th1-type cytokines released by immunoinflammatory T cells in the lesion.
authors.affiliation: Department of Neurology, Julius-Maximilians-Universität Würzburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Gold
authors.forename: K V
authors.initials: KV
authors.lastname: Toyka
authors.forename: H P
authors.initials: HP
authors.lastname: Hartung
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017951:Antigen Presentation / Q000187:drug effects* / Q000276:immunology; D051792:Basic Helix-Loop-Helix Proteins; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000276:immunology; D004357:Drug Synergism; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D051381:Rats; D011917:Rats, Inbred Lew; D012583:Schwann Cells / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C095572:Hand1 protein, mouse