Zeka Bleranda, Lassmann Hans, Bradl Monika
Department for Neuroimmunology Center for Brain Research Medical University Vienna Vienna Austria.
Clin Exp Neuroimmunol. 2017 Jan;8(Suppl Suppl 1):3-7. doi: 10.1111/cen3.12345. Epub 2017 Jan 11.
Recent work from our laboratory, using different models of experimental neuromyelitis optica spectrum disorder (NMOSD), has led to a number of observations that might be highly relevant for NMOSD patients. For example: (i) in the presence of neuromyelitis optica immunoglobulin G, astrocyte-destructive lesions can be initiated by CD4+ T cells when these cells recognize aquaporin 4 (AQP4), but also when they recognize other antigens of the central nervous system. The only important prerequisite is that the T cells have to be activated within the central nervous system by "their" specific antigen. Recently activated CD4+ T cells with yet unknown antigen specificity are also found in human NMOSD lesions. (ii) The normal immune repertoire might contain AQP4-specific T cells, which are highly encephalitogenic on activation. (iii) The retina might be a primary target of AQP4-specific T cells and neuromyelitis optica immunoglobulin G: AQP4-specific T cells alone are sufficient to cause retinitis with low-grade axonal pathology in the retinal nerve fiber/ganglionic cell layer. A thinning of these layers is also observed in NMOSD patients, where it is thought to be a consequence of optic neuritis. Neuromyelitis optica immunoglobulin G might target cellular processes of Müller cells and cause their loss of AQP4 reactivity, when AQP4-specific T cells open the blood-retina barrier in the outer plexiform layer. Patchy loss of AQP4 reactivity on Müller cells of NMOSD patients has been recently described. Cumulatively, our findings in experimental NMOSD suggest that both CD4+ T cell and antibody responses directed against AQP4 might play an important role in the pathogenesis of tissue destruction seen in NMOSD.
我们实验室最近的研究工作，使用了不同的实验性视神经脊髓炎谱系障碍（NMOSD）模型，得出了一些可能与NMOSD患者高度相关的观察结果。例如：（i）在存在视神经脊髓炎免疫球蛋白G的情况下，当CD4 + T细胞识别水通道蛋白4（AQP4）时，星形胶质细胞破坏性病变可以由这些细胞引发，但当它们识别中枢神经系统的其他抗原时也会引发。唯一重要的前提是T细胞必须在中枢神经系统内被“其”特定抗原激活。在人类NMOSD病变中也发现了具有未知抗原特异性的最近激活的CD4 + T细胞。（ii）正常的免疫库可能包含AQP4特异性T细胞，这些细胞在激活时具有高度致脑炎性。（iii）视网膜可能是AQP4特异性T细胞和视神经脊髓炎免疫球蛋白G的主要靶点：单独的AQP4特异性T细胞足以在视网膜神经纤维/神经节细胞层引起伴有低度轴突病理的视网膜炎。在NMOSD患者中也观察到这些层的变薄，据认为这是视神经炎的结果。当AQP4特异性T细胞打开外丛状层的血视网膜屏障时，视神经脊髓炎免疫球蛋白G可能靶向Müller细胞的细胞过程并导致其AQP4反应性丧失。最近已描述了NMOSD患者Müller细胞上AQP4反应性的斑片状丧失。累积起来，我们在实验性NMOSD中的发现表明，针对AQP4的CD4 + T细胞和抗体反应可能在NMOSD中所见的组织破坏发病机制中起重要作用。
