VLA-4/CD49d downregulated on primed T lymphocytes during interferon-beta therapy in multiple sclerosis.
Effects on adhesion molecules of immune cells might contribute to the mode of action of interferon-beta (IFN-beta) in multiple sclerosis (MS). We have serially monitored the cell surface expression of integrins CD49d (VLA-4) and CD11a (LFA-1) on fresh T lymphocyte subpopulations from 5 MS patients monthly for 2 months prior to treatment and for 3 months on treatment with IFN-beta1b. In parallel, we assessed inflammatory disease activity by monthly contrast-enhanced magnetic resonance imaging (MRI). IFN-beta treatment specifically downregulated CD49d expression on CD8+ and CD4+/CD45RO+ 'memory' T lymphocytes and differentially modulated the proportion of CD4+, CD8+ and CD27+ T cells. These effects may play an important role in the reduction of central nervous system cell trafficking and inflammation in MS.
Muraro
P A
PA
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive MSC1400, 20892-1400, Bethesda, MD, USA. pmuraro@umich.it
Leist
T
T
Bielekova
B
B
McFarland
H F
HF
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers; D015704:CD4 Antigens / Q000032:analysis; D018968:CD58 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D039441:Integrin alpha4; D039041:Integrin alpha4beta1; D019012:Integrin beta1 / Q000032:analysis; D016023:Integrins / Q000276:immunology / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D016899:Interferon-beta / Q000008:administration & dosage*; D017493:Leukocyte Common Antigens / Q000032:analysis; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology*; D016201:Receptors, Lymphocyte Homing / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D015415:Biomarkers; D015704:CD4 Antigens; D018968:CD58 Antigens; D016827:CD8 Antigens; D006684:HLA-DR Antigens; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D018799:Intercellular Adhesion Molecule-1; D039441:Integrin alpha4; D016899:Interferon-beta; D017493:Leukocyte Common Antigens