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干眼症中效应T细胞的特征分析

Characterization of effector T cells in dry eye disease.

作者信息

El Annan Jaafar, Chauhan Sunil K, Ecoiffier Tatiana, Zhang Qiang, Saban Daniel R, Dana Reza

机构信息

Schepens Eye Research Institute, Boston, MA 02114, USA.

出版信息

Invest Ophthalmol Vis Sci. 2009 Aug;50(8):3802-7. doi: 10.1167/iovs.08-2417. Epub 2009 Apr 1.

Abstract

PURPOSE

Dry eye disease (DED) is associated with ocular surface inflammation that is thought to be mediated primarily by CD4 T cells. The purpose of this study was to investigate whether this T cell-mediated immune response is generated in the lymphoid compartment and to characterize the functional phenotype of the T cells activated in DED.

METHODS

DED was induced in female C57BL/6 mice by exposure to a desiccating environment in the controlled environment chamber and to systemic scopolamine. T cells from regional draining lymph nodes (LNs) of DED mice and normally sighted mice were analyzed for surface activation markers (CD69 and CD154), chemokine and cytokine receptors, and proliferation potential.

RESULTS

Draining LNs of DED mice showed increased frequencies of CD69- and CD154-expressing T cells with higher proliferative capacity. In addition, these LN T cells primarily showed a helper T-cell (Th)1 phenotype, expressing significantly higher levels of IFN-gamma and IL-12Rbeta2 but not IL-4R. Similarly, the LNs of DED mice showed significantly increased frequencies of T cells expressing CXCR3 and CCR5, but not CCR4, suggesting a bias toward a Th1 phenotype.

CONCLUSIONS

These data demonstrate that a Th1-type immune response is induced in the regional LNs of DED mice. The identification of specific cytokine/chemokine receptors overexpressed by these T cells may signify potential novel targets/strategies for the treatment of DED.

摘要

目的

干眼症(DED)与眼表炎症相关,这种炎症被认为主要由CD4 T细胞介导。本研究的目的是调查这种T细胞介导的免疫反应是否在淋巴组织中产生,并表征在DED中被激活的T细胞的功能表型。

方法

通过在可控环境舱中暴露于干燥环境和全身给予东莨菪碱,在雌性C57BL/6小鼠中诱导出DED。分析来自DED小鼠和正常视力小鼠的区域引流淋巴结(LN)中的T细胞的表面激活标志物(CD69和CD154)、趋化因子和细胞因子受体以及增殖潜力。

结果

DED小鼠的引流LN显示出表达CD69和CD154的T细胞频率增加,且增殖能力更高。此外,这些LN T细胞主要表现为辅助性T细胞(Th)1表型,表达显著更高水平的IFN-γ和IL-12Rβ2,但不表达IL-4R。同样,DED小鼠的LN显示出表达CXCR3和CCR5的T细胞频率显著增加,但不表达CCR4,表明偏向Th1表型。

结论

这些数据表明在DED小鼠的区域LN中诱导了Th1型免疫反应。这些T细胞过度表达的特定细胞因子/趋化因子受体的鉴定可能意味着治疗DED的潜在新靶点/策略。

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Characterization of effector T cells in dry eye disease.干眼症中效应T细胞的特征分析
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