拉森氏脑炎的特征是在疱疹病毒感染时，IFN-β 和细胞毒性 T 细胞的产生相对较低。
Rasmussen's encephalitis is characterized by relatively lower production of IFN-β and activated cytotoxic T cell upon herpes viruses infection.
机构信息
Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, 100093, China.
出版信息
J Neuroinflammation. 2022 Mar 26;19(1):70. doi: 10.1186/s12974-022-02379-0.
BACKGROUND
The etiology of Rasmussen's encephalitis (RE), a rare chronic neurological disorder characterized by CD8+ T cell infiltration and unihemispheric brain atrophy, is still unknown. Various human herpes viruses (HHVs) have been detected in RE brain, but their contribution to RE pathogenesis is unclear.
METHODS
HHVs infection and relevant immune response were compared among brain tissues from RE, temporal lobe epilepsy (TLE) and traumatic brain injury (TBI) patients. Viral antigen or genome, CD8+ T cells, microglia and innate immunity molecules were analyzed by immunohistochemical staining, DNA dot blot assay or immunofluorescence double staining. Cytokines were measured by multiplex flow cytometry. Cell apoptosis was visualized by TUNEL staining. Viral infection, immune response and the severity of unihemispheric atrophy were subjected to correlation analysis.
RESULTS
Antigens of various HHVs were prevalent in RE and TLE brains, and the cumulative viral score of HHVs positively correlated with the unihemispheric atrophy in RE patients. CD8+ T cells infiltration were observed in both RE and TLE brains and showed co-localization with HHV antigens, but their activation, as revealed by Granzyme B (GZMB) release and apoptosis, was found only in RE. In comparison to TLE, RE brain tissues contained higher level of inflammatory cytokines, but the interferon-β level, which was negatively correlated with cumulative viral score, was relatively lower. In line with this, the DNA sensor STING and IFI16, rather than other innate immunity signaling molecules, were insufficiently activated in RE.
CONCLUSIONS
Compared with TBI, both RE and TLE had prevalently HHV infection and immune response in brain tissues. However, in comparison to TLE, RE showed insufficient activation of antiviral innate immunity but overactivation of cytotoxic T cells. Our results show the relatively lower level of antiviral innate immunity and overactivation of cytotoxic T cells in RE cases upon HHV infection, the overactivated T cells might be a compensate to the innate immunity but the causative evidence is lack in our study and need more investigation in the future.
背景
Rasmussen 脑炎（RE）是一种罕见的慢性神经疾病，其特征为 CD8+T 细胞浸润和单侧脑萎缩，其病因仍不清楚。在 RE 脑内已检测到各种人类疱疹病毒（HHV），但其对 RE 发病机制的贡献尚不清楚。
方法
比较了 RE、颞叶癫痫（TLE）和创伤性脑损伤（TBI）患者脑组织中的 HHVs 感染和相关免疫反应。通过免疫组化染色、DNA 斑点印迹分析或免疫荧光双染色分析病毒抗原或基因组、CD8+T 细胞、小胶质细胞和固有免疫分子。通过多重流式细胞术测量细胞因子。通过 TUNEL 染色可视化细胞凋亡。对病毒感染、免疫反应和单侧脑萎缩的严重程度进行相关性分析。
结果
各种 HHVs 的抗原在 RE 和 TLE 脑中普遍存在，HHV 的累积病毒评分与 RE 患者的单侧脑萎缩呈正相关。在 RE 和 TLE 脑内均观察到 CD8+T 细胞浸润，并与 HHV 抗原共定位，但仅在 RE 中观察到其激活，表现为颗粒酶 B（GZMB）释放和凋亡。与 TLE 相比，RE 脑组织中含有更高水平的炎症细胞因子，但干扰素-β水平相对较低，与累积病毒评分呈负相关。与此一致的是，在 RE 中，DNA 传感器 STING 和 IFI16，而不是其他固有免疫信号分子，激活不足。
结论
与 TBI 相比，RE 和 TLE 脑组织中均普遍存在 HHV 感染和免疫反应。然而，与 TLE 相比，RE 表现出抗病毒固有免疫激活不足，但细胞毒性 T 细胞过度激活。我们的研究结果表明，在 HHV 感染后，RE 病例中抗病毒固有免疫水平相对较低，细胞毒性 T 细胞过度激活，但在我们的研究中缺乏因果证据，需要进一步研究。
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