Autoantibody-boosted T-cell reactivation in the target organ triggers manifestation of autoimmune CNS disease
Autoantibody-boosted T-cell reactivation in the target organ triggers manifestation of autoimmune CNS disease
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DOI：
10.1073/pnas.1519608113
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发表时间：
2016-03-22
影响因子：
11.1
通讯作者：
Fluegel, Alexander
中科院分区：
文献类型：
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作者：
Flach, Anne-Christine;Litke, Tanja;Fluegel, Alexander
多发性硬化症（MS）是由对脑抗原有反应的T细胞引起的。在实验性自身免疫性脑脊髓炎（MS的动物模型）中，髓鞘反应性T细胞在进入神经组织时启动自身免疫过程，并在局部遇到其同源CNS抗原时重新激活。因此，CNS组织内T细胞再活化过程的强度对于临床疾病的表现和严重程度至关重要。最近，B细胞被发现参与中枢神经系统自身免疫的发病机制，与几个不同的潜在机制正在讨论中。我们在此报告B细胞在促进CNS自身免疫的起始过程中起重要作用。自身反应性B细胞在外周活化后产生的髓鞘特异性抗体与最初侵入的致病性T细胞一起扩散到CNS中。抗体在常驻抗原呈递吞噬细胞中积累，并显著增强了传入效应T细胞的活化。随之而来的强烈的血脑屏障破坏和免疫细胞募集导致临床疾病的快速表现。因此，髓鞘少突胶质细胞糖蛋白（MOG）特异性自身抗体可以通过与自身反应性T细胞合作帮助它们识别自身抗原并在免疫剥夺的神经组织内有效地重新激活来引发疾病发作。
Multiple sclerosis (MS) is caused by T cells that are reactive for brain antigens. In experimental autoimmune encephalomyelitis, the animal model for MS, myelin-reactive T cells initiate the autoimmune process when entering the nervous tissue and become reactivated upon local encounter of their cognate CNS antigen. Thereby, the strength of the T-cellular reactivation process within the CNS tissue is crucial for the manifestation and the severity of the clinical disease. Recently, B cells were found to participate in the pathogenesis of CNS autoimmunity, with several diverse underlying mechanisms being under discussion. We here report that B cells play an important role in promoting the initiation process of CNS autoimmunity. Myelin-specific antibodies produced by autoreactive B cells after activation in the periphery diffused into the CNS together with the first invading pathogenic T cells. The antibodies accumulated in resident antigen-presenting phagocytes and significantly enhanced the activation of the incoming effector T cells. The ensuing strong blood-brain barrier disruption and immune cell recruitment resulted in rapid manifestation of clinical disease. Therefore, myelin oligodendrocyte glycoprotein (MOG)-specific autoantibodies can initiate disease bouts by cooperating with the autoreactive T cells in helping them to recognize their autoantigen and become efficiently reactivated within the immune-deprived nervous tissue.