The 'immunological-synapse' at its APC side in relapsing and secondary-progressive multiple sclerosis: modulation by interferon-beta.
Reciprocal interactions between T cells and antigen-presenting cells (APCs) within the 'Immunological-Synapse' (IS) govern immune cell autoreactivity in multiple sclerosis (MS). The present study examined the expression of a range of co-stimulatory molecules: CD40, CD54, CD80, CD86 and HLA-DR, on the cell-surface of CD14(+) peripheral blood monocytes (PBM) from relapsing-remitting (RR) and secondary-progressive (SP)-MS patients, prior to and during 1 year of Interferon (IFN)-beta-1a (Rebif(R)) therapy. Prior to treatment, patients from both MS subtypes expressed elevated CD80 and reduced CD40 levels in comparison to controls. CD86 expression was significantly reduced in SP compared to RR patients and controls. IFN-beta therapy led to a significant reduction in the expression of CD54 and CD80 in both groups of patients as well as to elevation of CD40 and CD86 expression in SP patients. These results confirm IFN-mediated modulation of the APC surface within the immunological-synapse and implicate CD80 and CD86 as targets for interventional therapies in MS as well as other Th1-mediated autoimmune diseases.
Immunology Research Unit, Carmel Medical Center, 7 Michal Street, Haifa 34362, Israel.
Sarah
S
Shapiro
Yanina
Y
Galboiz
Nitza
N
Lahat
Amalia
A
Kinarty
Ariel
A
Miller
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D015703:Antigens, CD / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000096:biosynthesis; D002450:Cell Communication / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D020528:Multiple Sclerosis, Chronic Progressive / Q000276:immunology* / Q000628:therapy*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology* / Q000628:therapy*; D015854:Up-Regulation / Q000276:immunology
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497964:CD86 protein, human; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D018799:Intercellular Adhesion Molecule-1; D016899:Interferon-beta; D000068556:Interferon beta-1a