Migration of T-cell subsets in multiple sclerosis and the effect of interferon-b1a Introduction Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) of unknown aetiology. Neuropathologically, the dis- ease is characterized by perivascular infiltrates in the CNS. Detailed histopathological work has revealed four distinct subtypes of lesions, which are in part dominated by CD8+ T cells rather than CD4+ T cells (1). In addition, myelin-specific CD8+ T cells have been isolated from MS patients and healthy individuals (2, 3). For the development of inflammatory lesions lymphocytes migrate across the basal lamina surrounding the brain microvessels. The migration of T lymphocytes into the CNS depends on several factors including adhesion molecule expression on the blood–brain barrier and lymphocytes, chemoattraction and matrix metalloproteinases (MMPs) expression that allows the opening of the basal lamina by invading cells (4). Using in vitro models, an increased migration of peripheral blood mononu- clear cells (PBMC) derived from relapsing–remit- ting MS (RRMS) patients in comparison with healthy individuals has been observed. The import- ance of lymphocyte migration in the pathogenesis of MS has been stressed by the finding that the blockade of adhesion molecules by natalizumab reduces relapse rate and disability progression in MS (5, 6). Interferon-b (IFN-b) is one of the immunomodulatory treatments available for patients with RRMS. Its mechanism of action includes a cytokine shift towards TH2-type cytok- ines (7), in addition it has been suggested to directly stabilize the blood–brain barrier (8) and is known to reduce the migratory capacity of PBMC in vitro by suppression of MMP-9 production (9). MMP-9 has previously been shown to be produced by both CD4+ and CD8+ T cells (10). Cross- sectional studies of IFN-b-treated RRMS patients revealed a transient decrease of PBMC migration ex vivo, but no association with disease activity was detected (11, 12). A longitudinal study showed a trend towards lower migration of PBMC but failed to demonstrate statistically significant differences (13). To date no information is available which Acta Neurol Scand 2007: 116: 164–168 DOI: 10.1111/j.1600-0404.2007.00829.x Copyright Ó 2007 The Authors Journal compilation Ó 2007 Blackwell Munksgaard ACTA NEUROLOGICA SCANDINAVICA Dressel A, Mirowska-Guzel D, Gerlach C, Weber F. Migration of T-cell subsets in multiple sclerosis and the effect of interferon-b1a Acta Neurol Scand 2007: 116: 164–168. Ó 2007 The Authors Journal compilation Ó 2007 Blackwell Munksgaard. Objectives – Migration of inflammatory cells across the blood–brain barrier is a central event in the formation of multiple sclerosis (MS) lesions and is known to be enhanced in MS patients. This study investigates the migration of CD4+ and CD8+ T-cell subsets and the effects of interferon-b1a (IFN-b1a) treatment on migration and matrix metalloproteinase-9 (MMP-9) production of these T-cell subsets. Materials and methods – An ex vivo transwell system was established to compare the migratory behaviour of lymphocytes isolated from normal controls and untreated MS patients. In addition, MS patients were investigated longitudinally after initiation of IFN- b1a treatment. Results – Migration of CD4+ T cells (P < 0.05), but not of CD8+ T cells, was enhanced in untreated MS patients compared with controls and was normalized by treatment with IFN- b1a. In addition, IFN-b1a treatment reduced MMP-9 production of CD4+ but not CD8+ T cells. Conclusion – Our results indicate that CD4+ T cells, but not CD8+ T cells, contribute to the enhanced ex vivo migration observed in MS. A. Dressel 1 , D. Mirowska-Guzel 2 *, C. Gerlach 1 , F. Weber 2 1 Department of Neurology, University of Greifswald, Greifswald, Germany; 2 Section of Neurology, Max- Planck-Institute of Psychiatry, Munich, Germany Key words: multiple sclerosis; lymphocytes; migration; interferon-b; T cells; CD4+ T cells; CD8+ T cells Alexander Dressel, Department of Neurology, University Greifswald, Sauerbruchstr, 17475 Greifswald, Germany. Tel.: +49 3834 866839 Fax: +49 3834 866845 e-mail: adressel@neurologie.uni-greifswald.de *Present address: Department of Experimental and Clinical Pharmacology, Krakowskie Przedmies'cie 26/28, Medical University of Warsaw, 00-927 Warsaw, Poland. Accepted for publication 22 January 2007 164