Synergistic effect of IFN-gamma and TNF-alpha on expression of immune molecules and antigen presentation by Schwann cells.
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.
Gold
R
R
Department of Neurology, Julius-Maximilians-Universität Würzburg, Germany.
Toyka
K V
KV
Hartung
H P
HP
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*
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