Ono Hirohiko, Misu Tatsuro, Namatame Chihiro, Matsumoto Yuki, Takai Yoshiki, Nishiyama Shuhei, Kuroda Hiroshi, Takahashi Toshiyuki, Nakashima Ichiro, Fujihara Kazuo, Aoki Masashi
Department of Neurology, Tohoku University Graduate School of Medicine, Sendai 980-0845, Japan.
Department of Neurology, National Hospital Organization Yonezawa National Hospital, Yonezawa 992-1202, Japan.
Int J Mol Sci. 2025 Apr 11;26(8):3606. doi: 10.3390/ijms26083606.
To clarify T-cell responses in myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), we cultured the peripheral blood mononuclear cells of 24 patients with MOGAD and 20 with aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorders (NMOSD), and those of 17 healthy controls (HCs), in the presence of fourteen MOG peptides covering the full-length MOG, five AQP4 peptides, two myelin basic protein peptides, or two proteolipid protein peptides. Then, we measured T-cell activation markers, such as cell surface CD69 and the intracellular production of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-γ in CD4-positive T-cells, with a flow cytometer. The expression of CD69 in response to MOG p16-40 and MOG p181-205 was significantly higher (Stimulation Index > 2) in MOGAD than in HCs. Also, CD69 for AQP4 p21-40, AQP4 p211-230, and MOG p166-190 were significantly increased in NMOSD than in HCs. Intracellular GM-CSF production responding to MOG p16-40 was significantly higher in MOGAD than in HCs ( < 0.05), although intracellular interferon-γ was not elevated. None of the responses to the other peptides were different between the groups. The present study showed subtle CD4-positive T-cell activation elicited by some MOG peptides alone in patients with MOGAD. Further studies of cytokines or other stimulation and alternative assay markers and metrics are needed to delineate the immunopathological roles of T-cells in MOGAD.
为阐明髓鞘少突胶质细胞糖蛋白（MOG）抗体相关疾病（MOGAD）中的T细胞反应，我们培养了24例MOGAD患者、20例水通道蛋白4（AQP4）抗体阳性的视神经脊髓炎谱系障碍（NMOSD）患者以及17名健康对照（HC）的外周血单个核细胞，培养时加入覆盖全长MOG的14种MOG肽、5种AQP4肽、2种髓鞘碱性蛋白肽或2种蛋白脂蛋白肽。然后，我们用流式细胞仪检测T细胞活化标志物，如细胞表面CD69以及CD4阳性T细胞中粒细胞巨噬细胞集落刺激因子（GM-CSF）和干扰素-γ的细胞内产生情况。与健康对照相比，MOGAD患者对MOG p16-40和MOG p181-205反应时CD69的表达显著更高（刺激指数>2）。此外，与健康对照相比，NMOSD患者对AQP4 p21-40、AQP4 p211-230和MOG p166-190的CD69显著增加。尽管细胞内干扰素-γ未升高，但MOGAD患者对MOG p16-40反应时细胞内GM-CSF的产生显著高于健康对照（<0.05）。各组对其他肽的反应均无差异。本研究表明，MOGAD患者仅由某些MOG肽单独引发了细微的CD4阳性T细胞活化。需要进一步研究细胞因子或其他刺激以及替代检测标志物和指标，以阐明T细胞在MOGAD中的免疫病理作用。
