Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, USA.
Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi, USA.
Neuroimmunomodulation. 2019;26(4):198-207. doi: 10.1159/000501765. Epub 2019 Aug 27.
The active experimental autoimmune encephalomyelitis (EAE) model is often initiated using myelin oligodendrocyte glycoprotein (MOG) immunization followed by pertussis toxin (PTX) to study multiple sclerosis. However, PTX inactivates G protein-coupled receptors, and with increasing knowledge of the role that various G protein-coupled receptors play in immune homeostasis, it is valuable to establish neuroimmune endpoints for active EAE without PTX.
Female C57BL/6 mice were immunized with MOG35-55 peptide in Complete Freund's Adjuvant and neuroinflammation, including central nervous system B-cell infiltration, was compared to saline-injected mice. Since it was anticipated that disease onset would be slower and less robust than EAE in the presence of PTX, both cervical and lumbosacral sections of the spinal cord were evaluated.
Immunohistochemical analysis showed that EAE without PTX induced immune infiltration, CCL2 and VCAM-1 upregulation. Demyelination in the cervical region correlated with the infiltration of CD19+ B cells in the cervical region. There was upregulation of IgG, CD38, and PDL1 on B cells in cervical and lumbosacral regions of the spinal cord in EAE without PTX. Interestingly, IgG was expressed predominantly by CD19- cells.
These data demonstrate that many neuroimmune endpoints are induced in EAE without PTX and although clinical disease is mild, this can be used as an autoimmune model when PTX inactivation of G protein-coupled receptors is not desired.
实验性自身免疫性脑脊髓炎（EAE）模型通常采用髓鞘少突胶质细胞糖蛋白（MOG）免疫接种，然后用百日咳毒素（PTX）进行诱导，以研究多发性硬化症。然而，PTX 会使 G 蛋白偶联受体失活，随着人们对各种 G 蛋白偶联受体在免疫稳态中作用的认识不断增加，建立无 PTX 的主动 EAE 的神经免疫终点非常有价值。
雌性 C57BL/6 小鼠用 MOG35-55 肽在完全弗氏佐剂中免疫，比较神经炎症，包括中枢神经系统 B 细胞浸润，与盐水注射小鼠的情况。由于预计在没有 PTX 的情况下，疾病的发作会比 EAE 更缓慢且不那么严重，因此评估了颈椎和腰骶段脊髓的切片。
免疫组织化学分析显示，无 PTX 的 EAE 诱导了免疫浸润、CCL2 和 VCAM-1 的上调。颈椎区域的脱髓鞘与颈椎区域 CD19+B 细胞的浸润相关。无 PTX 的 EAE 中，颈椎和腰骶段脊髓的 B 细胞上 IgG、CD38 和 PDL1 上调。有趣的是，IgG 主要由 CD19-细胞表达。
这些数据表明，无 PTX 的 EAE 诱导了许多神经免疫终点，尽管临床疾病较轻，但当不希望 G 蛋白偶联受体失活时，可将其用作自身免疫模型。
