Seo Jincheol, Park Junghyung, Kim Keonwoo, Won Jinyoung, Yeo Hyeon-Gu, Jin Yeung Bae, Koo Bon-Sang, Lim Kyung Seob, Jeong Kang-Jin, Kang Philyong, Lee Hwal-Yong, Choi Won Seok, Baek Seung Ho, Jeon Chang-Yeop, Hong Jung-Joo, Huh Jae-Won, Kim Young-Hyun, Park Sang Je, Kim Sun-Uk, Lee Dong-Seok, Lee Sang-Rae, Lee Youngjeon
National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea; School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea.
National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju 28116, Republic of Korea.
Neuroscience. 2020 Apr 1;431:73-85. doi: 10.1016/j.neuroscience.2020.01.043. Epub 2020 Feb 7.
Study of interactions between the nervous system and immunity offers insights into the pathogenesis of Parkinson's disease (PD) and potential therapeutic strategies for neurodegenerative diseases. Studies on rodents have revealed regulatory mechanisms of microglial activation and T lymphocyte recruitment in PD. However, the mechanisms underlying chronic T lymphocyte infiltration into the brain after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injection into a non-human primate (NHP) model of PD remain unknown. This study aimed to investigate changes in serum RANTES (regulated on activation, normal T cell expression and secretion) and analyze the chronic infiltration of T lymphocytes into the brain and microglia activation in NHPs at 48 weeks post-MPTP administration. We found selective and local chronic infiltration of CD4+ and CD8+ T lymphocytes, loss of dopaminergic neurons, dopamine transporter expression, chronic normalization of RANTES in the peripheral blood, and altered microglial morphology at 48 weeks after MPTP injection. This study confirms the involvement of CD4+ and CD8+ T lymphocyte infiltration in MPTP-induced NHP models of PD. Additionally, we corroborated previous findings regarding the mechanisms of T lymphocyte-induced neurodegeneration. The findings of chronic infiltration of T lymphocytes in our NHP model of PD provide novel insights into PD pathogenesis and the development of preventive and therapeutic agents.
神经系统与免疫系统相互作用的研究为帕金森病(PD)的发病机制及神经退行性疾病的潜在治疗策略提供了见解。对啮齿动物的研究揭示了PD中微胶质细胞激活和T淋巴细胞募集的调节机制。然而,在将1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)注射到非人类灵长类动物(NHP)PD模型后,慢性T淋巴细胞浸润到大脑中的潜在机制仍不清楚。本研究旨在调查血清调节激活正常T细胞表达和分泌因子(RANTES)的变化,并分析MPTP给药后48周时NHP中T淋巴细胞向大脑的慢性浸润及小胶质细胞激活情况。我们发现在MPTP注射后48周时,CD4+和CD8+ T淋巴细胞存在选择性和局部慢性浸润、多巴胺能神经元丧失、多巴胺转运体表达、外周血RANTES慢性正常化以及小胶质细胞形态改变。本研究证实了CD4+和CD8+ T淋巴细胞浸润参与了MPTP诱导的NHP PD模型。此外,我们证实了先前关于T淋巴细胞诱导神经退行性变机制的研究结果。我们在NHP PD模型中T淋巴细胞慢性浸润的研究结果为PD发病机制以及预防和治疗药物的开发提供了新的见解。