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首页> 外文期刊>Progress in brain research >T cell-based therapeutic vaccination for spinal cord injury.
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T cell-based therapeutic vaccination for spinal cord injury.

机译：基于T细胞的脊髓损伤治疗性疫苗接种。

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Spinal cord injury results in a massive loss of neurons, due not only to the direct effects of the primary injury but also to self-destructive processes triggered by the insult. Our group has recently reported that traumatic injury of the central nervous system (CNS) spontaneously evokes a purposeful T cell-mediated autoimmune response that reduces the injury-induced degeneration in the CNS; in its absence, the outcome of the injury is worse. Using a rat model of spinal cord contusion, we show here that this autoimmune protection can be induced and/or boosted by post-traumatic immunization with CNS myelin-associated self antigens such as myelin basic protein (MBP). In an attempt to reduce the risk of pathogenic autoimmunity while retaining the benefit of the immunization, we immunized spinally injured rats with MBP-derived peptides with attenuated pathogenic properties created by replacement of one amino acid in the T cell receptor-binding site. Immunization with these altered peptide ligands immediately after spinal cord contusion resulted in a significant improvement in recovery, assessed by locomotor activity in an open field. The feasibility of T cell-based vaccination, as opposed to vaccination mediated by antibodies for the treatment of nerve trauma, is further suggested by the relatively rapid onset of the T cell response following immunization. Such cell-mediated therapy is not only a way to evoke and boost a physiological remedy; it also has the advantage of being mediated by mobile cells, which can produce a variety of neurotrophic factors and cytokines in accordance with the tissue needs. T cells can also regulate other immune cells in a way that favors tissue maintenance and repair.
机译：脊髓损伤导致神经元大量损失，这不仅是由于原发性损伤的直接作用，还归因于伤害引发的自我毁灭过程。我们的小组最近报告说，中枢神经系统（CNS）的创伤性损伤会自发地引起有目的的T细胞介导的自身免疫反应，从而减少CNS损伤引起的变性。在没有它的情况下，伤害的后果更糟。使用大鼠脊髓挫伤模型，我们在这里显示可以通过与CNS髓磷脂相关的自身抗原（如髓磷脂碱性蛋白（MBP））进行创伤后免疫来诱导和/或加强这种自身免疫保护。为了降低致病性自身免疫的风险，同时又保留了免疫的益处，我们用MBP衍生肽对脊髓损伤的大鼠进行了免疫，MBP肽的致病特性减弱，这种肽是通过在T细胞受体结合位点替换一个氨基酸而产生的。脊髓挫伤后立即用这些改变的肽配体进行免疫可显着改善恢复，这是通过在开放领域中的运动活性来评估的。与通过抗体介导的疫苗治疗神经损伤的疫苗接种相反，基于T细胞的疫苗接种的可行性通过免疫后T细胞反应的相对较快的发作进一步得到了证明。这种细胞介导的疗法不仅是一种唤起和增强生理疗法的方法;它也具有由移动细胞介导的优势，可以根据组织需要产生多种神经营养因子和细胞因子。 T细胞还可以通过有利于组织维护和修复的方式调节其他免疫细胞。

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