Changes of regulatory T cells and FoxP3 gene expression in the aging process and its relationship with lung tumors in humans and mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>The percentage of CD4(+)CD25(+)CD127(low) Tregs 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, an elderly healthy group, a young tumor group, a middle-aged tumor group, and an elderly tumor group. The percentage of CD4(+)CD25(+)FoxP3(+) Tregs and the expression level of FoxP3 mRNA in splenocytes were determined in the six groups.</p><p><b>RESULTS</b>The percentage of peripheral CD4(+)CD25(+)CD127(low) 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(+)CD127(low) Tregs 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.</p><p><b>CONCLUSIONS</b>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.</p>

An association between immunosenescence and CD4(+)CD25(+) regulatory T cells: a systematic review / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Age-related increment of the prevalence of CD4(+)CD25(+) regulatory T (Treg) cells were described controversially, and whether such changes explain immune dysfunction in the elderly is still unclear. The aim of this systematic review is to evaluate the role of the Tregs in immunosenescence.</p><p><b>METHODS</b>Medline and manual searches were performed to identify all published epidemiological and animal studies investigating the efficacy of the association between immunosenescence and Treg cells.</p><p><b>RESULTS</b>It was founded that the frequency, phenotypic characteristics, and number/function of Tregs were altered significantly with aging. Medical conditions in individuals with advanced ageas well as apoptosis intensity of Treg cells had an impact on the accumulation of Tregs which in turn could deteriorate cytotoxic activity of CD8(+) T and NK cells and production of IL-2. The range of immune cells that could be suppressed by Treg cells was quite wide and covered CD4(+)CD25(+) T cells, NK cells, dendritic cells and even monocytes. These changes were observed both in humans and experimental animals. Besides, it was believed that frequency of Tregs increased with age and was accompanied by intensified suppressive activity for Tregs in patients, for example, with Alzheimer disease (AD) and Parkinson disease (PD). The impaired condition of CD4(+) T cells, so-called immunosenescence, rendered transplant recipients less responsive to an allogeneic kidney graft, an effect that was limited to transplant recipients who were aged over 60 years.</p><p><b>CONCLUSIONS</b>Treg cells are associated with immunosenescence. All these changes contribute to the aging-related decline of immune responses and lead to the higher risk of immune-mediated diseases, cancer or infections in aged individuals.</p>