Posttraumatic therapeutic vaccination with modified myelin self-antigen prevents complete paralysis while avoiding autoimmune disease
Posttraumatic therapeutic vaccination with modified myelin self-antigen prevents complete paralysis while avoiding autoimmune disease
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DOI：
10.1172/jci200112837
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发表时间：
2001-08-01
影响因子：
15.9
通讯作者：
Schwartz, M
中科院分区：
文献类型：
--
作者：
Hauben, E;Agranov, E;Schwartz, M
脊髓损伤会导致神经元大量丧失，从而导致功能丧失。我们最近报道，针对髓磷脂相关抗原的自身免疫 T 细胞的被动转移为严重受损的脊髓提供了有效的神经保护。研究发现 T 细胞被动转移的治疗时间窗至少为 1 周。在这里，我们证明基于创伤后 T 细胞的主动疫苗接种也具有神经保护作用。使用髓磷脂相关抗原（例如髓磷脂碱性蛋白（MBP））进行免疫可显着促进大鼠模型脊髓挫伤后的恢复。为了降低自身免疫性疾病的风险，同时保留免疫接种的益处，我们在严重不完全脊髓损伤后立即用 MBP 衍生的改变的肽配体对大鼠进行疫苗接种。通过旷场行为测试评估，用这些肽进行免疫可以显着防止神经元损失，从而减少瘫痪程度。红核脊髓束的逆行标记和磁共振成像支持了行为结果。非致病性髓磷脂衍生肽的进一步优化有望引导开发有效的治疗性疫苗接种方案，作为预防不完全脊髓损伤后完全瘫痪的策略。
Spinal cord injury results in a massive loss of neurons, and thus of function. We recently reported that passive transfer of autoimmune T cells directed against myelin-associated antigens provides acutely damaged spinal cords with effective neuroprotection. The therapeutic time window for the passive transfer of T cells was found to be at least 1 week. Here we show that posttraumatic T cell-based active vaccination is also neuroprotective. Immunization with myelin-associated antigens such as myelin basic protein (MBP) significantly promoted recovery after spinal cord contusion injury in the rat model. To reduce the risk of autoimmune disease while retaining the benefit of the immunization, we vaccinated the rats immediately after severe incomplete spinal cord injury with MBP-derived altered peptide ligands. Immunization with these peptides resulted in significant protection from neuronal loss and thus in a reduced extent of paralysis, assessed by an open-field behavioral test. Retrograde labeling of the rubrospinal tracts and magnetic resonance imaging supported the behavioral results. Further optimization of nonpathogenic myelin-derived peptides can be expected to lead the way to the development of an effective therapeutic vaccination protocol as a strategy for the prevention of total paralysis after incomplete spinal cord injury.