Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Vienna, Austria.
Department of Epileptology, University Hospital Bonn, Bonn, Germany.
Epilepsia. 2021 Jun;62(6):1343-1353. doi: 10.1111/epi.16914. Epub 2021 May 6.
Medial temporal lobe epilepsy (MTLE) is a drug-resistant focal epilepsy that can be caused by a broad spectrum of different inciting events, including tumors, febrile seizures, and viral infections. In human epilepsy surgical resections as well as in animal models, an involvement of the adaptive immune system was observed. We here analyzed the presence of T cells in various subgroups of MTLE. We aimed to answer the question of how much inflammation was present and whether the presence of T cells was associated with seizures or associated with hippocampal neurodegeneration.
We quantified the numbers of CD3 T cells and CD8 cytotoxic T cells in the hippocampus of patients with gangliogliomas (GGs; intrahippocampal and extrahippocampal, with and without sclerosis), febrile seizures, and postinfectious encephalitic epilepsy and compared this with Rasmussen encephalitis, Alzheimer disease, and normal controls.
We could show that T cell numbers were significantly elevated in MTLE compared to healthy controls. CD3 as well as CD8 T cell numbers, however, varied highly among MTLE subgroups. By comparing GG patients with and without hippocampal sclerosis (HS), we were able to show that T-cell numbers were increased in extrahippocampal GG patients with hippocampal neuronal loss and HS, whereas extrahippocampal GG cases without hippocampal neuronal loss (i.e., absence of HS) did not differ from healthy controls. Importantly, T cell numbers in MTLE correlated with the degree of neuronal loss, whereas no correlation with seizure frequency or disease duration was found. Finally, we found that in nearly all MTLE groups, T cell numbers remained elevated even years after the inciting event.
We here provide a detailed histopathological investigation of the involvement of T cells in various subgroups of MTLE, which suggests that T cell influx correlates to neuronal loss rather than seizure activity.
内侧颞叶癫痫（MTLE）是一种耐药性局灶性癫痫，可由多种不同的诱发因素引起，包括肿瘤、热性惊厥和病毒感染。在人类癫痫手术切除和动物模型中，适应性免疫系统均参与其中。我们在此分析了各种 MTLE 亚组中 T 细胞的存在情况。我们旨在回答以下问题：炎症程度如何，T 细胞的存在是否与癫痫发作有关，或者是否与海马神经退行性变有关。
我们定量分析了神经节细胞瘤（GG；海马内和海马外，伴或不伴硬化）、热性惊厥和感染后脑炎性癫痫患者海马中 CD3 T 细胞和 CD8 细胞毒性 T 细胞的数量，并将其与 Rasmussen 脑炎、阿尔茨海默病和正常对照组进行比较。
与健康对照组相比，我们发现 MTLE 患者的 T 细胞数量显著升高。然而，CD3 和 CD8 T 细胞数量在 MTLE 亚组中差异很大。通过比较伴有和不伴有海马硬化（HS）的 GG 患者，我们发现伴有海马神经元丢失和 HS 的海马外 GG 患者的 T 细胞数量增加，而无海马神经元丢失的海马外 GG 病例（即无 HS）与健康对照组无差异。重要的是，MTLE 中的 T 细胞数量与神经元丢失程度相关，而与癫痫发作频率或疾病持续时间无关。最后，我们发现，在几乎所有 MTLE 组中，即使在诱发事件发生多年后，T 细胞数量仍保持升高。
我们在此对 T 细胞在各种 MTLE 亚组中的参与情况进行了详细的组织病理学研究，结果表明 T 细胞浸润与神经元丢失而非癫痫活动相关。
