Redox balance of mouse medullary CD4 single-positive thymocytes
Redox balance of mouse medullary CD4 single-positive thymocytes
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DOI：
10.1038/icb.2013.57
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发表时间：
2013-11-01
影响因子：
4
通讯作者：
Ge, Qing
中科院分区：
文献类型：
--
作者：
Jin, Rong;Teng, Fei;Ge, Qing
经过阳性选择后，新分化的单阳性(SP)胸腺细胞经过阴性选择以消除自身反应性T细胞，功能成熟以获得免疫活性和出口能力。为了探讨细胞内氧化还原平衡是否在SP成熟过程中起重要作用，比较了代表SP分化程序的四个亚群小鼠胸腺细胞(SP1-SP4)的细胞内活性氧(ROS)水平及其调节ROS的蛋白质表达。在SP成熟过程中，ROS逐渐增加，硫氧还蛋白逐渐减少。成熟的SP阶段的高ROS水平并不是由于自然调节性T细胞和SP胸腺细胞在经历负选择(Helios阳性)的这一阶段的特定富集性所致。在最成熟的SP4细胞中，ROS的增加导致刺激后细胞因子的产生增加，而在未成熟的SP1胸腺细胞中，ROS的早期增加导致细胞凋亡的增加。AIRE(-/-)小鼠在负选择方面有缺陷，在SP3-SP4转换中存在发育障碍，其SP3胸腺细胞中的ROS显著减少。胸腺上皮细胞在体外能促进SP的成熟，也能增加SP胸腺细胞的ROS水平。这些结果提示，ROS可能参与了促进CD_4~(+)SP功能成熟的过程，胸腺髓质微环境可能参与了SP胸腺细胞的氧化前移。
After positive selection, the newly differentiated single-positive (SP) thymocytes undergo negative selection to eliminate autoreactive T cells, functional maturation to acquire immunocompetence and egress capability. To investigate whether the intracellular reduction/oxidation (redox) balance has an important role on SP maturation, the levels of intracellular reactive oxygen species (ROS) and the expression of proteins that regulate ROS were compared among the four subsets of mouse TCR alpha beta(+)CD4(+)CD8(-) thymocytes (SP1-SP4) that represent sequential stages of SP differentiation program. A gradual increase of ROS and a gradual decrease of thioredoxin were revealed along the SP maturation process. The high ROS level at the mature SP stage did not result from a specific enrichment at this stage of natural regulatory T cells and SP thymocytes undergoing negative selection (Helios positive). An increase of ROS in the most mature SP4 cells resulted in enhanced cytokine production upon stimulation, whereas an early increase of ROS in the immature SP1 thymocytes resulted in enhanced apoptosis. Aire(-/-) mice,that have defects in negative selection and a developmental blockage at the SP3-SP4 transition showed significantly less ROS in SP3 thymocytes. Thymic epithelial cells that have been shown to promote SP maturation in vitro also increased the ROS level of SP thymocytes. These results suggest that ROS may be involved in promoting the functional maturation of CD4(+) SPs and thymic medullary microenvironment contributes to the pro-oxidant shift of SP thymocytes.