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首页> 美国卫生研究院文献>other >Endogenous Interferon-β-Inducible Gene Expression and Interferon-β-Treatment Are Associated with Reduced T Cell Responses to Myelin Basic Protein in Multiple Sclerosis
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Endogenous Interferon-β-Inducible Gene Expression and Interferon-β-Treatment Are Associated with Reduced T Cell Responses to Myelin Basic Protein in Multiple Sclerosis

机译：内源性干扰素-β诱导基因表达和干扰素-β治疗与多发性硬化症中对髓鞘碱性蛋白的T细胞应答降低有关

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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.
机译：自身反应性CD4 + T细胞被认为在多发性硬化症的发病机理中起主要作用。在实验性自身免疫性脑脊髓炎中，多发性硬化，外源性和内源性I型干扰素的动物模型限制了疾病的严重程度。重组干扰素-β用于治疗多发性硬化症，一些未经治疗的多发性硬化症患者在免疫细胞中I型干扰素诱导型基因的表达水平增加。内源性I型干扰素在多发性硬化症中的作用是有争议的：一些研究发现，未经治疗的多发性硬化症患者中，高表达水平的干扰素-β诱导型基因与白介素10的表达增加以及病程较轻有关。研究报道与干扰素-β治疗反应差有关。在本研究中，我们发现未经治疗的多发性硬化症患者外周血单核细胞中干扰素-β诱导型基因表达增加，而干扰素-β治疗的多发性硬化症患者CD4 + T-降低离体对自身抗原髓鞘碱性蛋白的细胞反应性。干扰素-β治疗的多发性硬化症患者体内单核细胞中IL10和IL27基因表达水平升高。在体外，中和白细胞介素10和单核细胞耗竭可增加CD4 + T细胞对髓鞘碱性蛋白的反应性，而白细胞介素10在存在或不存在单核细胞的情况下抑制CD4 + T细胞对髓鞘碱性蛋白的反应性。我们的发现表明，未经治疗的多发性硬化症患者外周血单核细胞中干扰素-β诱导型基因的自发表达和干扰素-β的治疗与髓鞘碱性蛋白诱导的T细胞反应减少有关。干扰素-β治疗的多发性硬化症患者中髓鞘碱性蛋白诱导的CD4 + T细胞自身反应性降低可能是由单核细胞衍生的白介素10介导的。

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