title: Interferon-beta therapy reduces CD4+ and CD8+ T-cell reactivity in multiple sclerosis.
abstract: Therapy with interferon-beta (IFN-beta) 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-beta-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-beta. 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-beta 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-beta-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-beta therapy. Our data suggest that the beneficial effect of IFN-beta 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.
authors.affiliation: Biochemisches Institut, Infektiologie, Justus-Liebig-Universität Giessen, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Zafranskaya
authors.forename: Patrick
authors.initials: P
authors.lastname: Oschmann
authors.forename: Rosel
authors.initials: R
authors.lastname: Engel
authors.forename: Andreas
authors.initials: A
authors.lastname: Weishaupt
authors.forename: Johannes M
authors.initials: JM
authors.lastname: van Noort
authors.forename: Hassan
authors.initials: H
authors.lastname: Jomaa
authors.forename: Matthias
authors.initials: M
authors.lastname: Eberl
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D018450:Disease Progression; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D017493:Leukocyte Common Antigens / Q000097:blood; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology / Q000628:therapy*; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; C571326:MOG protein, human; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D016899:Interferon-beta; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1