title: Interferon-beta up-regulates the expression of co-stimulatory molecules CD80, CD86 and CD40 on monocytes: significance for treatment of multiple sclerosis.
abstract: Interferon (IFN)-beta reduces the biological activity of multiple sclerosis (MS), a presumably T cell-mediated autoimmune disease of central nervous system (CNS) myelin. Co-stimulatory molecules are necessary for full T cell activation and differential expression of co-stimulatory molecules on antigen-presenting cells is thought to influence the type of effector T cell response (Th1/Th2). In this study we investigated the effects of IFN-beta on the expression of co-stimulatory molecules on lymphocytes and monocytes as a potential mechanism of action of IFN-beta in MS. Peripheral blood mononuclear cells (PBMCs) were stimulated with IFN-beta in vitro and expression of CD80, CD86, CD40 and HLA was examined by flow cytometry and reverse-transcription polymerase chain reaction. Whereas IFN-beta had no effect on the expression of these molecules on T and B lymphocytes there was a significant increase on monocytes. Correspondingly, the expression of mRNA increased after 6-18 h. This in vitro response was also observed in untreated MS patients and patients receiving treatment with IFN-beta. The increase of co-stimulatory molecules on monocytes was not mediated by interleukin (IL)-10. When IFN-beta-stimulated monocytes were used to stimulate autologous T cells an increased secretion of IL-13 was observed. In biopsies taken from IFN-beta-induced skin reactions after subcutaneous injection increased expression of CD80 mRNA was detected, indicating that IFN-beta also up-regulates this co-stimulatory molecule in vivo. These data provide the background for further studies of IFN-beta-induced changes of co-stimulatory molecules in MS patients.
authors.affiliation: Department of Neurology, Medical School Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Marckmann
authors.forename: E
authors.initials: E
authors.lastname: Wiesemann
authors.forename: R
authors.initials: R
authors.lastname: Hilse
authors.forename: C
authors.initials: C
authors.lastname: Trebst
authors.forename: M
authors.initials: M
authors.lastname: Stangel
authors.forename: A
authors.initials: A
authors.lastname: Windhagen
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000032:analysis* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D018122:B7-1 Antigen / Q000032:analysis* / Q000276:immunology; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000032:analysis* / Q000276:immunology; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis / Q000276:immunology; D006801:Humans; D016899:Interferon-beta / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D009103:Multiple Sclerosis / Q000276:immunology*; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013601:T-Lymphocytes; D015854:Up-Regulation / Q000276:immunology
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D016753:Interleukin-10; D016899:Interferon-beta