Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, OR, USA.
Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, USA.
Ann Clin Transl Neurol. 2021 Feb;8(2):456-470. doi: 10.1002/acn3.51303. Epub 2021 Jan 13.
To determine whether animals with Japanese macaque encephalomyelitis (JME), a spontaneous demyelinating disease similar to multiple sclerosis (MS), harbor myelin-specific T cells in their central nervous system (CNS) and periphery.
Mononuclear cells (MNCs) from CNS lesions, cervical lymph nodes (LNs) and peripheral blood of Japanese macaques (JMs) with JME, and cervical LN and blood MNCs from healthy controls or animals with non-JME conditions were analyzed for the presence of myelin-specific T cells and changes in interleukin 17 (IL-17) and interferon gamma (IFNγ) expression.
Demyelinating JME lesions contained CD4 T cells and CD8 T cells specific to myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP), and/or proteolipid protein (PLP). CD8 T-cell responses were absent in JME peripheral blood, and in age- and sex-matched controls. However, CD4 Th1 and Th17 responses were detected in JME peripheral blood versus controls. Cervical LN MNCs from eight of nine JME animals had CD3 T cells specific for MOG, MBP, and PLP that were not detected in controls. Mapping myelin epitopes revealed a heterogeneity in responses among JME animals. Comparison of myelin antigen sequences with those of JM rhadinovirus (JMRV), which is found in JME lesions, identified six viral open reading frames (ORFs) with similarities to myelin antigen sequences. Overlapping peptides to these JMRV ORFs did not induce IFNγ responses.
JME possesses an immune-mediated component that involves both CD4 and CD8 T cells specific for myelin antigens. JME may shed new light on inflammatory demyelinating disease pathogenesis linked to gamma-herpesvirus infection.
确定是否患有日本猕猴脑炎（JME）的动物——一种类似于多发性硬化症（MS）的自发性脱髓鞘疾病——在其中枢神经系统（CNS）和外周组织中存在髓鞘特异性 T 细胞。
分析 JME 猕猴 CNS 病变、颈淋巴结（LN）和外周血的单核细胞（MNC）、健康对照或非 JME 动物的颈 LN 和血液 MNC 中是否存在髓鞘特异性 T 细胞以及白细胞介素 17（IL-17）和干扰素 γ（IFNγ）表达的变化。
脱髓鞘 JME 病变包含针对髓鞘少突胶质细胞糖蛋白（MOG）、髓鞘碱性蛋白（MBP）和/或蛋白脂质蛋白（PLP）的 CD4 T 细胞和 CD8 T 细胞。JME 外周血和年龄及性别匹配的对照中不存在 CD8 T 细胞反应。然而，JME 外周血中检测到 CD4 Th1 和 Th17 反应，而对照中未检测到。对 9 只 JME 动物中的 8 只颈 LN MNC 的分析显示，存在针对 MOG、MBP 和 PLP 的 CD3 T 细胞，而对照中未检测到。髓鞘表位作图显示 JME 动物之间存在反应异质性。将髓鞘抗原序列与 JME 病变中发现的 JM 风疹病毒（JMRV）的序列进行比较，确定了与髓鞘抗原序列具有相似性的 6 个病毒开放阅读框（ORF）。这些 JMRV ORF 的重叠肽未诱导 IFNγ 反应。
JME 具有涉及髓鞘抗原的 CD4 和 CD8 T 细胞的免疫介导成分。JME 可能为与γ疱疹病毒感染相关的炎症性脱髓鞘疾病发病机制提供新的线索。
