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Changes of regulatory T cells and FoxP3 gene expression in the aging process and its relationship with lung tumors in humans and mice

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Chinese Medical Journal 2012年第11期125卷 2004-2011页

作者： PAN Xu-dong MAO Yan-qing ZHU Li-jing LI Jie XIE Yan WANG Ling ZHANG Guang-bo Special Requirement Ward First Affiliated Hospital of Soochow University Suzhou Jiangsu 215006 China Clinical Immunology Laboratory First Affiliated Hospital of Soochow University Suzhou Jiangsu 215006 China

Background Immunosuppressive regulatory T cells （Tregs） participate in tumor immune evasion and the number and suppressive function of Tregs change with the aging process, but it is not clear whether such change leads to a higher incidence of tumors in the elderly. To this end, we designed experiments to explore the changes of Tregs and the functional gene Forkhead box P3 （FoxP3） in the aging process and its relationship with lung tumors in humans and mice. Methods The percentage of CD4＋CD25＋CD127lowTregs and expression of FoxP3 mRNA were analyzed using flow cytometry （FCM） and real-time fluorescence-based quantitative polymerase chain reaction （FQ-PCR）. Markers were analyzed in the peripheral blood （PB） of 65 elderly patients （age 〉-65 years） with primary non-small cell lung cancer （NSCLC）, 20 younger patients （aged 〈55 years） with NSCLC, 30 elderly healthy individuals and 30 young healthy individuals. Furthermore, we set up the Lewis lung cancer model with C57BL/6 female mice. Thirty-six mice were divided into a young healthy group, a middle-aged healthy group, tumor group, and an elderly tumor group. The percentage an elderly healthy group, a young tumor group, a middle-aged of CD4＋CD25＋FoxP3＋ Tregs and the expression level of FoxP3 mRNA in splenocytes were determined in the six groups. Results The percentage of peripheral CD4＋CD25＋CD127low Tregs and the expression of FoxP3 mRNA were significantly increased in elderly patients with NSCLC comparing with the other groups and in elderly healthy individuals compared with young healthy individuals. Further analysis showed that the percentage of CD4＋CD25＋CD127lowTregs and the expression of FoxP3 mRNA were closely associated with tumor node metastasis （TNM） staging in elderly patients with NSCLC. In the mouse model, the percentage of CD4＋CD25＋FoxP3＋ Tregs and the expression of FoxP3 mRNA in splenocytes of the tumor groups were significantly higher than in the healthy groups, with the highest expression in the elderly tu

关键词： aging regulatory Tcells CD127 FoxP3 immunosenescence, lung tumor

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