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

• Published in: Chinese medical journal 2012-06, Vol.125 (11), p.2004-2011
• Main Authors: Pan, Xu-Dong, Mao, Yan-Qing, Zhu, Li-Jing, Li, Jie, Xie, Yan, Wang, Ling, Zhang, Guang-Bo
• Format: Article
• Language: English
• Subjects: Aging - genetics; Aging - metabolism; Animals; CD4 Antigens - metabolism; Female; Flow Cytometry; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Humans; Interleukin-2 Receptor alpha Subunit - metabolism; Interleukin-7 Receptor alpha Subunit - metabolism; Lung Neoplasms - immunology; Lung Neoplasms - metabolism; Mice; Mice, Inbred C57BL; mRNA表达水平; Real-Time Polymerase Chain Reaction; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; 人类; 基因表达; 肺肿瘤; 荧光定量聚合酶链反应; 衰老过程; 调节性T细胞; 雌性小鼠
• ISSN: 0366-6999; 2542-5641
• DOI: 10.3760/cma.j.issn.0366-6999.2012.11.030

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 tumor group. In the healthy groups, the elderly healthy mice had the highest percentage of Tregs and expression of FoxP3 mRNA. The elderly mice had larger and heavier tumors than did the young and middle aged mice. Conclusions The up-regulation of Tregs and the FoxP3 gene with aging may play an essential role in oncogenesis and development of lung tumors in an elderly population.