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

• Published in: PloS one 2015-03, Vol.10 (3)
• Main Authors: Börnsen, Lars, Romme Christensen, Jeppe, Ratzer, Rikke, Hedegaard, Chris, Søndergaard, Helle B, Krakauer, Martin, Hesse, Dan, Nielsen, Claus H, Sorensen, Per S, Sellebjerg, Finn
• Format: Article
• Language: English
• Subjects: Analysis; Care and treatment; Gene expression; Genetic aspects; Health aspects; Interferon beta; Multiple sclerosis; Physiological aspects; T cells
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0118830

Autoreactive CD4.sup.+ 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-[beta] 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-[beta]-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-[beta]. In the present study, we found that untreated multiple sclerosis patients with an increased expression of interferon-[beta]-inducible genes in peripheral blood mononuclear cells and interferon-[beta]-treated multiple sclerosis patients had decreased CD4.sup.+ T-cell reactivity to the autoantigen myelin basic protein ex vivo. Interferon-[beta]-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.sup.+ T-cell reactivity to myelin basic protein while interleukin-10, in the presence or absence of monocytes, inhibited CD4.sup.+ T-cell reactivity to myelin basic protein. Our findings suggest that spontaneous expression of interferon-[beta]-inducible genes in peripheral blood mononuclear cells from untreated multiple sclerosis patients and treatment with interferon-[beta] are associated with reduced myelin basic protein-induced T-cell responses. Reduced myelin basic protein-induced CD4.sup.+ T-cell autoreactivity in interferon-[beta]-treated multiple sclerosis patients may be mediated by monocyte-derived interleukin-10.