Endogenous interferon-?-inducible gene expression and interferon-?-treatment are associated with reduced T cell responses to myelin basic protein in multiple sclerosis.

ABSTRACT: 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-? 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-?-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-?. In the present study, we found that untreated multiple sclerosis patients with an increased expression of interferon-?-inducible genes in peripheral blood mononuclear cells and interferon-?-treated multiple sclerosis patients had decreased CD4+ T-cell reactivity to the autoantigen myelin basic protein ex vivo. Interferon-?-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-?-inducible genes in peripheral blood mononuclear cells from untreated multiple sclerosis patients and treatment with interferon-? are associated with reduced myelin basic protein-induced T-cell responses. Reduced myelin basic protein-induced CD4+ T-cell autoreactivity in interferon-?-treated multiple sclerosis patients may be mediated by monocyte-derived interleukin-10.

SUBMITTER: Bornsen L 

PROVIDER: S-EPMC4349448 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature