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Interferon-β therapy reduces CD4+ and CD8+ T-cell reactivity in multiple sclerosis

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Author: Zafranskaya, M. · Oschmann, P. · Engel, R. · Weishaupt, A. · Noort, J.M. van · Jomaa, H. · Eberl, M.
Type:article
Date:2007
Institution: TNO Kwaliteit van Leven
Source:Immunology, 1, 121, 29-39
Identifier: 239948
doi: doi:10.1111/j.1365-2567.2006.02518.x
Keywords: Health · Biomedical Research · Autoimmunity · CFSE (5- (and 6-) carboxyfluorescein diacetate succinimidyl ester) · Disease progression · Immunotherapy · Myelin antigens · T-cell responses · beta1a interferon · CD45RO antigen · cytokine · interferon beta serine · myelin oligodendrocyte glycoprotein · adult · article · CD4+ T lymphocyte · CD8+ T lymphocyte · cell proliferation · clinical article · controlled study · correlation analysis · drug response · ex vivo study · female · functional status · human · human cell · immunotherapy · in vitro study · male · memory cell · multiple sclerosis · phenotype · prevalence · priority journal · Adult · Antigens, CD45 · CD4-Positive T-Lymphocytes · CD8-Positive T-Lymphocytes · Cell Proliferation · Cells, Cultured · Cytokines · Disease Progression · Flow Cytometry · Humans · Immunologic Memory · Immunophenotyping · Immunosuppressive Agents · Interferon-beta · Lymphocyte Activation · Middle Aged · Multiple Sclerosis, Relapsing-Remitting · Myelin-Associated Glycoprotein · T-Lymphocyte Subsets

Abstract

Therapy with interferon-β (IFN-β) has well-established clinical effects in multiple sclerosis (MS), albeit the immunomodulatory mechanisms are not fully understood. We assessed the prevalence and functional capacity of CD4+ and CD8+ T cells in healthy donors, and in untreated and IFN-β-treated MS patients, in response to myelin oligodendrocyte glycoprotein (MOG). The proportion of CD45RO+ memory T cells was higher in MS patients than in healthy donors, but returned to normal values upon therapy with IFN-β. While CD45RO+ CD4+ T cells from all three groups responded to MOG in vitro, untreated patients showed augmented proliferative responses compared to healthy individuals and IFN-β treatment reduced this elevated reactivity back to the values observed in healthy donors. Similarly, the response of CD45RO+ CD8+ T cells to MOG was strongest in untreated patients and decreased to normal values upon immunotherapy. Overall, the frequency of peripheral CD45RO+ memory T cells ex vivo correlated with the strength of the cellular in vitro response to MOG in untreated patients but not in healthy donors or IFN-β-treated patients. Compared with healthy individuals, responding CD4+ and CD8+ cells were skewed towards a type 1 cytokine phenotype in untreated patients, but towards a type 2 phenotype under IFN-β therapy. Our data suggest that the beneficial effect of IFN-β in MS might be the result of the suppression or depletion of autoreactive, pro-inflammatory memory T cells in the periphery. Assessment of T-cell subsets and their reactivity to MOG may represent an important diagnostic tool for monitoring successful immunotherapy in MS. © 2007 Blackwell Publishing Ltd.