Stroke induces a rapid adaptive autoimmune response to novel neuronal antigens.
Stroke induces a rapid adaptive autoimmune response to novel neuronal antigens.
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发表时间：
2015-05
影响因子：
1.4
通讯作者：
Sterling B Ortega;Ibrahim Noorbhai;Katherine Poinsatte;Xiangmei Kong;Ashley G. Anderson;N. Monson;A. Stowe
中科院分区：
文献类型：
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作者：
Sterling B Ortega;Ibrahim Noorbhai;Katherine Poinsatte;Xiangmei Kong;Ashley G. Anderson;N. Monson;A. Stowe
中风每年影响全世界数百万人。尽管如此，缺血性脑内的长期损伤和修复机制仍然研究不足。无菌性炎症发生在中风后受损的大脑中，受损的组织暴露出中枢神经系统（CNS）衍生的抗原，可能引发潜在的自身免疫反应。我们使用了一个标准的免疫学为基础的回忆反应试验的小鼠免疫细胞，从颈部淋巴结和脾脏分离短暂中风后，以确定中风是否诱导自身反应性中枢神经系统的靶抗原。我们的试验包括新的神经元肽，除了髓磷脂，核，神经胶质细胞和内皮细胞衍生的肽。基于非刺激条件下的增殖和活化，认为对抗原的自身免疫应答为阳性。早在卒中发作后4天，卒中诱导自身反应性CD 4+和CD 8 + T细胞以及自身反应性CD 19 + B细胞显著增加。在从淋巴结而非脾脏分离的细胞中，具有大梗死体积的小鼠表现出早期T和B细胞对NR2A（NMDA受体亚基）的自身反应性。小梗死体积的小鼠表现出对MAP 2（一种树突状细胞骨架蛋白）以及髓鞘衍生肽的高自身反应性。中风后10天，所有淋巴细胞亚群的淋巴结和脾脏中的自身免疫性都保持不变。假手术也诱导早期自身反应性B细胞对MAP 2和髓磷脂的反应。基于这些观察结果，我们假设中风诱导了一种继发的、复杂的、动态的对神经元抗原的自身免疫反应，这种反应有可能增强，甚至可能改善长期的神经炎症。
Stroke affects millions of people worldwide every year. Despite this prevalence, mechanisms of long-term injury and repair within the ischemic brain are still understudied. Sterile inflammation occurs in the injured brain after stroke, with damaged tissue exposing central nervous system (CNS)-derived antigen that could initiate potential autoimmune responses. We used a standard immunology-based recall response assay for murine immune cells, isolated from the cervical lymph nodes and spleen after transient stroke, to determine if stroke induces autoreactivity to CNS target antigens. Our assays included novel neuronal peptides, in addition to myelin-, nuclear-, glial-, and endothelial-derived peptides. Autoimmune responses to an antigen were considered positive based on proliferation and activation over non-stimulated conditions. Stroke induced a significant increase in autoreactive CD4+ and CD8+ T cells, as well as autoreactive CD19+ B cells, as early as 4 days after stroke onset. Mice with large infarct volumes exhibited early T and B cell autoreactivity to NR2A, an NMDA receptor subunit, in cells isolated from lymph nodes but not spleen. Mice with small infarct volumes exhibited high autoreactivity to MAP2, a dendritic cytoskeletal protein, as well as myelin-derived peptides. This autoimmunity was maintained through 10 days post-stroke in both lymph nodes and spleen for all lymphocyte subsets. Sham surgery also induced early autoreactive B cell responses to MAP2 and myelin. Based on these observations, we hypothesize that stroke induces a secondary, complex, and dynamic autoimmune response to neuronal antigens with the potential to potentiate, or perhaps even ameliorate, long-term neuroinflammation.