Interferon-beta therapy reduces CD4+ and CD8+ T-cell reactivity in multiple sclerosis |
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| Authors: | Zafranskaya Marina Oschmann Patrick Engel Rosel Weishaupt Andreas van Noort Johannes M Jomaa Hassan Eberl Matthias |
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| Affiliation: | Biochemisches Institut, Infektiologie, Justus-Liebig-Universit?t Giessen, Germany. |
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| 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. |
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| Keywords: | autoimmunity CFSE (5- (and 6-) carboxyfluorescein diacetate succinimidyl ester) disease progression immunotherapy myelin antigens T-cell responses |
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