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有益 T 细胞的神经面貌:在大脑中必不可少,在衰老和神经系统疾病中受损,并被神经递质和神经肽功能性激活

英文原题:Neuro faces of beneficial T cells: essential in brain, impaired in aging and neurological diseases, and activated functionally by neurotransmitters and neuropeptides.

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Neuro faces of beneficial T cells: essential in brain, impaired in aging and neurological diseases, and activated functionally by neurotransmitters and neuropeptides.

PubMed 2023/06/01(内容时间) Neural Regen Res Q1 · IF 8.5(JCR 2025)

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中文摘要

T 细胞对健康生命至关重要,持续执行:免疫监视、识别、保护、激活、抑制、辅助、清除、分泌、黏附、迁移、归巢、通讯以及其他任务。本文描述了正常有益 T 细胞在健康或患病大脑中的五个方面。第一,正常有益 T 细胞对正常健康脑功能至关重要:认知、空间学习、记忆、成年神经发生和神经保护。T 细胞减少继发性神经元变性,增加中枢神经系统(CNS)损伤后的神经元存活,并限制损伤和感染时的 CNS 炎症和损害。第二,虽然致病性 T 细胞促进 CNS 疾病,但近期研究(主要在动物模型中)显示,正常有益 T 细胞的特定亚群在多种神经炎症性和神经退行性疾病中具有保护和再生作用。这些疾病包括多发性硬化(MS)、阿尔茨海默病、帕金森病、肌萎缩侧索硬化(ALS)、卒中、CNS 创伤、慢性疼痛等。T 细胞分泌的分子和直接的细胞-细胞接触均传递 T 细胞的神经保护、神经再生和免疫调节作用。第三,正常有益 T 细胞在衰老和多种神经系统疾病中异常、受损和功能障碍。不同的 T 细胞损伤在衰老、脑肿瘤(主要为胶质母细胞瘤)、严重病毒感染(包括 COVID-19)、慢性应激、重性抑郁、精神分裂症、帕金森病、阿尔茨海默病、ALS、MS、卒中和其他神经病理中表现明显。

损害 T 细胞功能的主要有害机制是活化诱导的细胞死亡、耗竭、衰老和 T 细胞干性受损。第四,几种生理性神经递质和神经肽本身通过其在T细胞上的受体,对正常人类T细胞诱导多种直接、强效、有益且具有治疗相关性的效应。这一科学领域被称为“神经驱动免疫”。对初始正常人类T细胞直接诱导激活和有益效应的主要神经递质和神经肽包括:多巴胺、谷氨酸、GnRH-II、神经肽Y、降钙素基因相关肽和生长抑素。第五,“个性化过继神经免疫治疗”。这是一种基于“神经驱动免疫”发现的新型独特细胞免疫疗法,最近被设计并申请专利,用于通过将任何有需要者的T细胞在体外暴露于神经递质和神经肽,安全且反复地 rejuvenation、激活和改善其受损和功能失调的T细胞。个性化过继神经免疫治疗包括早期体外个性化诊断,以及随后根据诊断定制的体外→体内个性化过继治疗。个性化过继神经免疫治疗尚未在人体中进行测试,尚待临床试验验证其安全性和有效性,尤其是在脑肿瘤、慢性感染性疾病和衰老中,这些情况下T细胞耗竭和/或衰老且功能失调。

展开英文摘要原文

T cells are essential for a healthy life, performing continuously: immune surveillance, recognition, protection, activation, suppression, assistance, eradication, secretion, adhesion, migration, homing, communications, and additional tasks. This paper describes five aspects of normal beneficial T cells in the healthy or diseased brain. First, normal beneficial T cells are essential for normal healthy brain functions: cognition, spatial learning, memory, adult neurogenesis, and neuroprotection. T cells decrease secondary neuronal degeneration, increase neuronal survival after central nervous system (CNS) injury, and limit CNS inflammation and damage upon injury and infection. Second, while pathogenic T cells contribute to CNS disorders, recent studies, mostly in animal models, show that specific subpopulations of normal beneficial T cells have protective and regenerative effects in several neuroinflammatory and neurodegenerative diseases. These include Multiple Sclerosis (MS), Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), stroke, CNS trauma, chronic pain, and others. Both T cell-secreted molecules and direct cell-cell contacts deliver T cell neuroprotective, neuroregenerative and immunomodulatory effects. Third, normal beneficial T cells are abnormal, impaired, and dysfunctional in aging and multiple neurological diseases. Different T cell impairments are evident in aging, brain tumors (mainly Glioblastoma), severe viral infections (including COVID-19), chronic stress, major depression, schizophrenia, Parkinson's disease, Alzheimer's disease, ALS, MS, stroke, and other neuro-pathologies.

The main detrimental mechanisms that impair T cell function are activation-induced cell death, exhaustion, senescence, and impaired T cell stemness. Fourth, several physiological neurotransmitters and neuropeptides induce by themselves multiple direct, potent, beneficial, and therapeutically-relevant effects on normal human T cells, via their receptors in T cells. This scientific field is called "Nerve-Driven Immunity". The main neurotransmitters and neuropeptides that induce directly activating and beneficial effects on naïve normal human T cells are: dopamine, glutamate, GnRH-II, neuropeptide Y, calcitonin gene-related peptide, and somatostatin. Fifth, "Personalized Adoptive Neuro-Immunotherapy".

This is a novel unique cellular immunotherapy, based on the "Nerve-Driven Immunity" findings, which was recently designed and patented for safe and repeated rejuvenation, activation, and improvement of impaired and dysfunctional T cells of any person in need, by ex vivo exposure of the person's T cells to neurotransmitters and neuropeptides.

Personalized adoptive neuro-immunotherapy includes an early ex vivo personalized diagnosis, and subsequent ex vivo → in vivo personalized adoptive therapy, tailored according to the diagnosis. The Personalized Adoptive Neuro-Immunotherapy has not yet been tested in humans, pending validation of safety and efficacy in clinical trials, especially in brain tumors, chronic infectious diseases, and aging, in which T cells are exhausted and/or senescent and dysfunctional.

论文信息

作者
Levite M
单位
Faculty of Medicine, The Hebrew University of Jerusalem, Campus Ein Karem; Institute of Gene Therapy, The Hadassah University Hospital -Ein Karem, Jerusalem, Israel.Israel
文献类型
综述
期刊
Neural regeneration research2023 Jun
原文标识
PubMed 36453390 · DOI 10.4103/1673-5374.357903