CD4 positive T helper cells contribute to retinal ganglion cell death in mouse model of ischemia reperfusion injury
CD4 positive T helper cells contribute to retinal ganglion cell death in mouse model of ischemia reperfusion injury
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DOI：
10.1016/j.exer.2013.06.015
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发表时间：
2013-10-01
影响因子：
3.4
通讯作者：
Zhang, Samuel S.
中科院分区：
文献类型：
--
作者：
Huang, Ping;Huo, Yanjiao;Zhang, Samuel S.
神经元变性是与包括视网膜在内的中枢神经系统中的许多疾病状况相关的常见病理过程。虽然免疫反应被认为是引发神经损伤的一个潜在因素，但发病机制中特定免疫成分的作用机制尚不清楚。在这项研究中，我们专注于适应性免疫活动，以评估视网膜神经节细胞（RGC）变性中的CD 4阳性辅助细胞对短暂性视网膜缺血/再灌注（I/R）损伤的反应。在4个具有不同免疫背景的小鼠品系中诱导短暂性视网膜缺血，包括来自C57 BL/6和BABL/c品系的野生型小鼠、缺乏T和B淋巴细胞的严重联合免疫缺陷（SCID）小鼠、转移野生型CD 4 + T细胞的SCID小鼠和没有辅助性T细胞2（TH 2）的STAT 6缺陷小鼠。在SCID小鼠中，与C57 BL/6（p = 0.018）和BALB/C（p = 0.038）野生型相比，RGCs对I/R损伤引起的细胞死亡表现出较强的抵抗力（对侧眼存活细胞的89% +/- 3%）。通过将匹配野生型的成熟CD 4 + T细胞转移到SCID小鼠中，RGCs对损伤的抵抗力显着降低（p < 0.05）。此外，与野生型对照相比，在响应I/R损伤的STAT 6缺陷小鼠中证实了RGC对细胞死亡的显著抗性（p < 0.05），伴随着STAT 1和STAT 3的过表达，表明TH 2细胞成熟可能参与RGC损伤。由CD 4 T细胞携带的适应性免疫在RGC变性中起重要作用。(C)2013爱思唯尔有限公司保留所有权利。
Neuron degeneration is a common pathological process associated with many disease conditions in the central nervous system including retina. Although immune responses have been proposed as one potential element in triggering neural damage, the mechanism of action of specific immune components underlying the pathogenesis is unclear. In this study we focus on adaptive immune activities to evaluate CD4 positive helper cells in the retinal ganglion cell (RGC) degeneration in response to transient retinal ischemic/reperfusion (I/R) injury. Transient retinal ischemia was induced in four mouse strains with different immune backgrounds, including wild type mice from C57BL/6 and BABL/c strains, severe combined immunodeficient (SCID) mice lacking T and B lymphocytes, SCID mice with transferred wild type CD4+ T cells, and the STAT6 deficient mice without T helper 2 (TH2) cells. In SCID mice RGCs showed a strong resistance to cell death in response to I/R injury (89% +/- 3% of the survival cells in contralateral eye) compared with C57BL/6 (p = 0.018) and BALB/C (p = 0.038) wild types. By transferring the mature CD4+ T cells from matched wild type into SCID mice, the resistance of RGCs to injury was significantly compromised (p < 0.05). Furthermore a significant resistance of RGCs to cell death (p < 0.05) accompanied with an overexpression of STAT1 and STAT3 was confirmed in STAT6 deficient mice in response to I/R injury compared with the wild type controls, indicating that TH2 cells maturation might be involved in RGC damage. Adaptive immunity carried by CD4 T cells plays an essential role in RGC degeneration. (C) 2013 Elsevier Ltd. All rights reserved.