Title
Interferon-β therapy reduces CD4+ and CD8+ T-cell reactivity in multiple sclerosis
Author
Zafranskaya, M.
Oschmann, P.
Engel, R.
Weishaupt, A.
van Noort, J.M.
Jomaa, H.
Eberl, M.
TNO Kwaliteit van Leven
Publication year
2007
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.
Subject
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
To reference this document use:
http://resolver.tudelft.nl/uuid:41eb19c2-44a2-4839-97da-368d12aeef93
DOI
https://doi.org/10.1111/j.1365-2567.2006.02518.x
TNO identifier
239948
ISSN
0019-2805
Source
Immunology, 121 (1), 29-39
Document type
article