Synergistic immune responses induced by endogenous retrovirus and herpesvirus antigens result in increased production of inflammatory cytokines in multiple sclerosis patients
Synergistic immune responses induced by endogenous retrovirus and herpesvirus antigens result in increased production of inflammatory cytokines in multiple sclerosis patients
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DOI：
10.1111/j.1365-3083.2007.02067.x
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发表时间：
2008-03-01
影响因子：
3.7
通讯作者：
Moller-Larsen, A.
中科院分区：
文献类型：
--
作者：
Brudek, T.;Christensen, T.;Moller-Larsen, A.
人内源性逆转录病毒（HERV）和疱疹病毒与神经炎症性疾病多发性硬化症（MS）的发病机制越来越相关。疱疹病毒能够激活 HERV，并且 HERV 和疱疹病毒抗原的同时存在对细胞介导的免疫反应具有协同作用，与健康个体相比，多发性硬化症患者的免疫反应往往更高。在这里，我们研究这些协同免疫反应是否反映在促炎细胞因子产生的变化中。使用酶联免疫吸附测定 (ELISA)，我们在 MS 患者和健康对照之间进行了比较研究，以研究 HERV 和疱疹抗原组合刺激的外周血单核细胞 (PBMC) 上清液中干扰素 (IFN)-γ、白细胞介素 (IL) 2 或 IL-10 的产生以及 Th1 和 Th2 反应之间的平衡。我们发现，由于 HERV 和疱疹抗原的共同存在，MS 患者的 PBMC 中 Th1/Th2 反应存在显着的不平衡。结果还显示，多发性硬化症患者的细胞中 IFN-γ 的产生显着增加；此外，这种产生与协同细胞增殖相关，而我们在健康对照中没有发现这种相关性。我们的研究结果表明，多发性硬化症患者中 IFN-γ 产生的增加和诱导的 Th1/Th2 反应失衡有利于炎症反应，可能会导致疾病进展。
Human endogenous retroviruses (HERV) and herpesviruses are increasingly associated with the pathogenesis of the neurological inflammatory disease multiple sclerosis (MS). Herpesviruses are capable of HERV activation and simultaneous presence of HERV and herpesvirus antigens have a synergistic effect on cell-mediated immune responses, which tend to be higher in MS patients in comparison with healthy individuals. Here, we investigate whether these synergistic immune responses are reflected in changes in the production of proinflammatory cytokines. Using enzyme-linked immunosorbent assays (ELISAs), we have performed a comparative study between MS patients and healthy controls to investigate the production of interferon (IFN)-gamma, interleukin (IL) 2, or IL-10 as well as the balance between Th1 and Th2 responses in supernatants from peripheral blood mononuclear cells (PBMC) stimulated with HERV and herpes antigen combinations. We have found a significant disproportion in Th1/Th2 responses in PBMCs from MS patients caused by the joint presence of HERV and herpes antigens. The results also showed a significantly higher IFN-gamma production in cells from MS patients; additionally, this production correlated with the synergistic cell proliferations whereas we did not find such a correlation in healthy controls. Our findings suggest that the increased production of IFN-gamma and the induced imbalance in Th1/Th2 responses favouring the inflammatory reactions in MS patients may lead to progression of the disease.