Interferon‐β up‐regulates the expression of co‐stimulatory molecules CD80, CD86 and CD40 on monocytes: significance for treatment of multiple sclerosis

• Published in: Clinical and experimental immunology Vol. 138; no. 3; pp. 499 - 506
• Main Authors: MARCKMANN, S., WIESEMANN, E., HILSE, R., TREBST, C., STANGEL, M., WINDHAGEN, A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.12.2004; Blackwell; Blackwell Science Inc
• Subjects: Adult; Antigens, CD - analysis; Antigens, CD - immunology; B-Lymphocytes - immunology; B7-1 Antigen - analysis; B7-1 Antigen - immunology; B7-2 Antigen; Biological and medical sciences; CD40 Antigens - analysis; CD40 Antigens - immunology; Cells, Cultured; Clinical Studies; co‐stimulatory molecules; Dose-Response Relationship, Immunologic; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; HLA-DR Antigens - analysis; HLA-DR Antigens - immunology; Humans; Immunopathology; Interferon-beta - immunology; interferon‐β; Interleukin-10 - immunology; Male; Medical sciences; Membrane Glycoproteins - analysis; Membrane Glycoproteins - immunology; Monocytes - immunology; multiple sclerosis; Multiple Sclerosis - immunology; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger; T-Lymphocytes; Up-Regulation - immunology; Immunopathology; Nervous system diseases; Multiple sclerosis; Monocyte; co-stimulatory molecules interferon-β multiple sclerosis; Costimulatory molecule; Inflammatory disease; B7-2 Molecule; Regulation(control); Immunology; Treatment; B7-1 Molecule; Central nervous system disease; Beta interferon
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2004.02624.x

SUMMARY Interferon (IFN)‐β 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‐β on the expression of co‐stimulatory molecules on lymphocytes and monocytes as a potential mechanism of action of IFN‐β in MS. Peripheral blood mononuclear cells (PBMCs) were stimulated with IFN‐β in vitro and expression of CD80, CD86, CD40 and HLA was examined by flow cytometry and reverse‐transcription polymerase chain reaction. Whereas IFN‐β 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‐β. The increase of co‐stimulatory molecules on monocytes was not mediated by interleukin (IL)‐10. When IFN‐β‐stimulated monocytes were used to stimulate autologous T cells an increased secretion of IL‐13 was observed. In biopsies taken from IFN‐β‐induced skin reactions after subcutaneous injection increased expression of CD80 mRNA was detected, indicating that IFN‐β also up‐regulates this co‐stimulatory molecule in vivo. These data provide the background for further studies of IFN‐β‐induced changes of co‐stimulatory molecules in MS patients.