Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Endogenous Interferon-β-Inducible Gene Expression and Interferon-β-Treatment Are Associated with Reduced T Cell Responses to Myelin Basic Protein in Multiple Sclerosis

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Novel functions of the luteinizing hormone/chorionic gonadotropin receptor in prostate cancer cells and patients

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Hepatitis C prevalence in Denmark in 2016-An updated estimate using multiple national registers

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Inflammation, non-endothelial dependent coronary microvascular function and diastolic function-Are they linked?

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Lipidomics of human adipose tissue reveals diversity between body areas

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Initial high-efficacy disease-modifying therapy in multiple sclerosis: A nationwide cohort study

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. MAIT cell subtypes in multiple sclerosis

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Amyloid transthyretinkardiomyopati

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Early Intrathecal T Helper 17.1 Cell Activity in Huntington Disease

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

Autoreactive CD4+ T-cells are considered to play a major role in the pathogenesis of multiple sclerosis. In experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, exogenous and endogenous type I interferons restrict disease severity. Recombinant interferon-β is used for treatment of multiple sclerosis, and some untreated multiple sclerosis patients have increased expression levels of type I interferon-inducible genes in immune cells. The role of endogenous type I interferons in multiple sclerosis is controversial: some studies found an association of high expression levels of interferon-β-inducible genes with an increased expression of interleukin-10 and a milder disease course in untreated multiple sclerosis patients, whereas other studies reported an association with a poor response to treatment with interferon-β. In the present study, we found that untreated multiple sclerosis patients with an increased expression of interferon-β-inducible genes in peripheral blood mononuclear cells and interferon-β-treated multiple sclerosis patients had decreased CD4+ T-cell reactivity to the autoantigen myelin basic protein ex vivo. Interferon-β-treated multiple sclerosis patients had increased IL10 and IL27 gene expression levels in monocytes in vivo. In vitro, neutralization of interleukin-10 and monocyte depletion increased CD4+ T-cell reactivity to myelin basic protein while interleukin-10, in the presence or absence of monocytes, inhibited CD4+ T-cell reactivity to myelin basic protein. Our findings suggest that spontaneous expression of interferon-β-inducible genes in peripheral blood mononuclear cells from untreated multiple sclerosis patients and treatment with interferon-β are associated with reduced myelin basic protein-induced T-cell responses. Reduced myelin basic protein-induced CD4+ T-cell autoreactivity in interferon-β-treated multiple sclerosis patients may be mediated by monocyte-derived interleukin-10.

Original languageEnglish
JournalP L o S One
Volume10
Issue number3
Pages (from-to)e0118830
ISSN1932-6203
DOIs
Publication statusPublished - 2015

ID: 45051008