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首页> 外文期刊>Journal of Pathology: Journal of the Pathological Society of Great Britain and Ireland >Surgical excision of CNS-draining lymph nodes reduces relapse severity in chronic-relapsing experimental autoimmune encephalomyelitis.
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Surgical excision of CNS-draining lymph nodes reduces relapse severity in chronic-relapsing experimental autoimmune encephalomyelitis.

机译：在慢性复发性实验性自身免疫性脑脊髓炎中，通过手术切除引流中枢神经系统的淋巴结可降低复发的严重程度。

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Despite lack of classical lymphatic vessels in the central nervous system (CNS), cells and antigens do reach the CNS-draining lymph nodes. These lymph nodes are specialized to mediate mucosal immune tolerance, but can also generate T- and B-cell immunity. Their role in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) therefore remains elusive. We hypothesized that drainage of CNS antigens to the CNS-draining lymph nodes is vital for the recurrent episodes of CNS inflammation. To test this, we surgically removed the superficial cervical lymph nodes, deep cervical lymph nodes, and the lumbar lymph nodes prior to disease induction in three mouse EAE models, representing acute, chronic, and chronic-relapsing EAE. Excision of the CNS-draining lymph nodes in chronic-relapsing EAE reduced and delayed the relapse burden and EAE pathology within the spinal cord, which suggests initiation of CNS antigen-specific immune responses within the CNS-draining lymph nodes. Indeed, superficial cervical lymph nodes from EAE-affected mice demonstrated proliferation against the immunizing peptide, and the deep cervical lymph nodes, lumbar lymph nodes, and spleen demonstrated additional proliferation against other myelin antigen epitopes. This indicates that intermolecular epitope spreading occurs and that CNS antigen-specific immune responses are differentially generated within the different CNS-draining lymphoid organs. Proliferation of splenocytes from lymphadenectomized and sham-operated mice against the immunizing peptide was similar. These data suggest a role for CNS-draining lymph nodes in the induction of detrimental immune responses in EAE relapses, and conclusively demonstrate that the tolerance-inducing capability of cervical lymph nodes is not involved in EAE.
机译：尽管中枢神经系统（CNS）中缺乏经典的淋巴管，但细胞和抗原确实到达了引流CNS的淋巴结。这些淋巴结专门用于介导粘膜免疫耐受，但也可以产生T细胞和B细胞免疫。因此，它们在多发性硬化症和实验性自身免疫性脑脊髓炎（EAE）中的作用仍然难以捉摸。我们假设将中枢神经系统抗原引流至中枢神经系统引流淋巴结对于中枢神经系统炎症复发发作至关重要。为了对此进行测试，我们在三种小鼠EAE模型（分别代表急性，慢性和慢性复发性EAE）中，通过手术切除了浅表颈淋巴结，深颈淋巴结和腰淋巴结，然后诱发疾病。慢性复发性EAE中CNS引流淋巴结的切除减少并延迟了脊髓内的复发负担和EAE病理，这提示了CNS引流淋巴结内CNS抗原特异性免疫反应的开始。实际上，来自受EAE影响的小鼠的浅颈淋巴结表现出针对免疫肽的增殖，而深颈淋巴结，腰淋巴结和脾脏表现出针对其他髓磷脂抗原表位的额外增殖。这表明发生了分子间表位扩散，并且在不同的CNS引流淋巴器官内差异产生了CNS抗原特异性免疫反应。来自淋巴结切除和假手术小鼠的脾细胞针对免疫肽的增殖是相似的。这些数据表明，引流中枢神经系统的淋巴结在EAE复发中有害的免疫反应的诱导中起作用，并最终证明宫颈淋巴结的耐受性诱导能力不参与EAE。

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