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树突状细胞调节抗 ICAM-1 抗体 MD-3 对常见狨猴实验性自身免疫性脑脊髓炎的抑制作用。

Attenuation of Experimental Autoimmune Encephalomyelitis in a Common Marmoset Model by Dendritic Cell-Modulating Anti-ICAM-1 Antibody, MD-3.

机构信息

Department of Neurology, Seoul National University Hospital, Seoul, Republic of Korea.

Neuroscience Research Institute, Seoul National University Medical Research Center, Seoul, Republic of Korea.

出版信息

Mol Neurobiol. 2019 Jul;56(7):5136-5145. doi: 10.1007/s12035-018-1438-5. Epub 2018 Nov 28.

Abstract

MD-3 is a novel anti-human ICAM-1 monoclonal antibody that induces T cell tolerance in humanized mice via modulation of dendritic cell differentiation and efficiently suppresses the development of collagen-induced arthritis. This effect has also been observed in xenograft rejection in nonhuman primates, where grafts survived for more than 2.5 years following MD-3 administration. Here, we show that MD-3 can attenuate experimental autoimmune encephalomyelitis (EAE) that was induced in common marmoset monkeys by immunization with human myelin oligodendrocyte glycoproteins. MD-3 administration was initiated 1 week after immunization and efficiently delayed the development of EAE phenotypes, although the disease was not completely prevented. Based on the results of histopathological examination, MD-3 treatment greatly suppressed total inflammation with respect to demyelination, as well as T cell and microglial infiltration in the brain. However, the antibody response against myelin oligodendrocyte glycoprotein was not suppressed with this treatment protocol. These observations suggest that the MD-3 antibody has beneficial effects on the treatment of EAE via the suppression of T cell-mediated cellular responses.

摘要

MD-3 是一种新型抗人细胞间黏附分子-1 单克隆抗体,可通过调节树突状细胞分化诱导人源化小鼠中的 T 细胞耐受,并有效抑制胶原诱导性关节炎的发展。在非人灵长类动物的异种移植物排斥中也观察到了这种效应,在给予 MD-3 后,移植物的存活时间超过 2.5 年。在这里,我们表明 MD-3 可以减轻用人类髓鞘少突胶质细胞糖蛋白免疫常见狨猴后诱导的实验性自身免疫性脑脊髓炎(EAE)。MD-3 给药在免疫后 1 周开始,并有效地延迟了 EAE 表型的发展,尽管疾病未完全预防。基于组织病理学检查的结果,MD-3 治疗极大地抑制了脱髓鞘、大脑中的 T 细胞和小胶质细胞浸润的总炎症。然而,用这种治疗方案并未抑制针对髓鞘少突胶质细胞糖蛋白的抗体反应。这些观察结果表明,MD-3 抗体通过抑制 T 细胞介导的细胞反应对 EAE 的治疗具有有益作用。

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