Differential effects of myelin basic protein-activated Th1 and Th2 cells on the local immune microenvironment of injured spinal cord

Differential effects of myelin basic protein-activated Th1 and Th2 cells on the local immune microenvironment of injured spinal cord
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髓磷脂碱性蛋白激活的Th1和Th2细胞对损伤脊髓局部免疫微环境的差异作用

DOI:
10.1016/j.expneurol.2016.01.002
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发表时间:
2016-03-01
影响因子:
5.3
通讯作者:
Lu, He-Zuo
Lu, He-Zuo
中科院分区:
医学2区
文献类型:
--
作者:
Hu, Jian-Guo;Shi, Ling-Ling;Lu, He-Zuo

文献摘要

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髓鞘碱性蛋白(MBP)激活的T细胞(MBP-T)在中枢神经系统(CNS)的损伤和修复过程中发挥着重要作用。然而,这些细胞发挥的是有益的还是有害的作用仍然是一个争论的问题。尽管有研究表明MBP-T细胞主要是辅助性T(Th)细胞,但其亚型仍不十分清楚。MBP-T免疫导致相互矛盾的结果的一个可能的解释可能是不同的T细胞亚型负责不同的效果。本研究通过体外极化Th1和Th2型MBP-T细胞(MBP-Th1和-Th2),探讨过继免疫对脊髓损伤局部免疫微环境和组织修复的影响。MBP-Th1细胞移植组大鼠损伤脊髓组织中存在高水平的促炎细胞(Th1细胞和M1巨噬细胞)和细胞因子TNF-γ、Tfn-α、-β、IL-1β,而MBP-Th2细胞移植组大鼠脊髓中存在抗炎细胞(Th2细胞、调节性T细胞和M2巨噬细胞)和细胞因子(IL-4、-10和-13)。MBP-Th2细胞转移导致损伤体积减少,轴突髓鞘形成增加,神经元得以保存。随之而来的是运动能力的显著改善。这些结果表明,MBP-Th2过继转移对损伤脊髓有一定的保护作用,Th2细胞数量的增加可能改变局部微环境,使局部微环境由以Th1、M1细胞为主转变为以Th2、Treg、M2细胞为主,有利于脊髓损伤的修复。(C)2016 Elsevier Inc.保留所有权利。
Myelin basic protein (MBP) activated T cells (MBP-T) play an important role in the damage and repair process of the central nervous system (CNS). However, whether these cells playa beneficial or detrimental role is still a matter of debate. Although some studies showed that MBP-T cells are mainly helper T (Th) cells, their subtypes are still not very clear. One possible explanation for MBP-T immunization leading to conflicting results may be the different subtypes of T cells are responsible for distinct effects. In this study, the Th1 and Th2 type MBP-T cells (MBP-Th1 and -Th2) were polarized in vitro, and their effects on the local immune microenvironment and tissue repair of spinal cord injury (SCI) after adoptive immunization were investigated. In MBP-Th1 cell transferred rats, the high levels of pro-inflammatory cells (Th1 cells and M1 macrophages) and cytokines TNF-gamma, TFN-alpha, -beta, IL-1 beta) were detected in the injured spinal cord; however, the anti-inflammatory cells (Th2 cells, regulatory T cells, and M2 macrophages) and cytokines (IL-4, -10, and -13) were found in MBP-Th2 cell transferred animals. MBP-Th2 cell transfer resulted in decreased lesion volume, increased myelination of axons, and preservation of neurons. This was accompanied by significant locomotor improvement. These results indicate that MBP-Th2 adoptive transfer has beneficial effects on the injured spinal cord, in which the increased number of Th2 cells may alter the local microenvironment from one primarily populated by Th1 and M1 cells to another dominated by Th2, Treg, and M2 cells and is conducive for SCI repair. (C) 2016 Elsevier Inc. All rights reserved.