IL-6-deficient mice are resistant to experimental autoimmune encephalomyelitis: roles of IL-6 in the activation and differentiation of autoreactive T cells.
IL-6-deficient mice are resistant to experimental autoimmune encephalomyelitis: roles of IL-6 in the activation and differentiation of autoreactive T cells.
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DOI：
10.4049/jimmunol.161.12.6480
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发表时间：
1998-12
影响因子：
4.4
通讯作者：
E. B. Samoilova;J. Horton;B. Hilliard;T. T. Liu-T.;Youhai H. Chen
中科院分区：
文献类型：
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作者：
E. B. Samoilova;J. Horton;B. Hilliard;T. T. Liu-T.;Youhai H. Chen
虽然识别自身髓鞘抗原的自身反应性T细胞存在于大多数个体中，但中枢神经系统的自身免疫性疾病是相对罕见的医学病症。自身免疫性疾病的发展可能不仅需要自身反应性T细胞的存在，而且需要自身反应性T细胞被激活。T细胞的活化可能需要至少两个信号：由MHC-肽复合物递送的Ag特异性信号和由共刺激分子或细胞因子递送的第二信号。尽管体外研究表明细胞因子，特别是促炎细胞因子如IL-1、IL-6和TNF参与T细胞活化，但它们在体内的确切作用尚不清楚。为了确定促炎细胞因子在体内T细胞活化和自身免疫性疾病发展中的作用，我们研究了IL-6缺陷小鼠的实验性自身免疫性脑脊髓炎（EAE）。我们发现，IL-6-缺陷的小鼠是完全抵抗髓鞘少突胶质细胞糖蛋白（MOG）诱导的EAE，而IL-6-主管控制小鼠发展EAE的特点是局灶性炎症和脱髓鞘的中枢神经系统和神经功能的缺陷。此外，我们确定IL-6缺陷小鼠对EAE的抵抗力与体内MOG特异性T细胞分化为Th 1或Th 2型效应细胞的缺陷有关。这些结果有力地表明，IL-6在体内自身反应性T细胞的活化和分化中起着至关重要的作用，并且阻断IL-6功能可以是预防EAE的有效手段。
Although autoreactive T cells recognizing self myelin Ags are present in most individuals, autoimmune disease of the central nervous system is a relatively rare medical condition. Development of autoimmune disease may require not only the presence of autoreactive T cells but also that autoreactive T cells become activated. Activation of T cells may require a minimum of two signals: an Ag-specific signal delivered by MHC-peptide complex and a second signal delivered by costimulatory molecules or cytokines. Although in vitro studies have suggested that cytokines, especially proinflammatory cytokines such as IL-1, IL-6, and TNF are involved in T cell activation, their precise roles in vivo are not clear. To determine the roles of proinflammatory cytokines in T cell activation in vivo and in the development of autoimmune disease, we have studied experimental autoimmune encephalomyelitis (EAE) in mice deficient in IL-6. We found that IL-6-deficient mice were completely resistant to EAE induced by myelin oligodendrocyte glycoprotein (MOG), whereas IL-6-competent control mice developed EAE characterized by focal inflammation and demyelination in the central nervous system and deficiency in neurologic functions. Furthermore, we established that the resistance to EAE in IL-6-deficient mice was associated with a deficiency of MOG-specific T cells to differentiate into either Th1 or Th2 type effector cells in vivo. These results strongly suggest that IL-6 plays a crucial role in the activation and differentiation of autoreactive T cells in vivo and that blocking IL-6 function can be an effective means to prevent EAE.