Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
PLoS One. 2012;7(1):e29250. doi: 10.1371/journal.pone.0029250. Epub 2012 Jan 3.
It is well-recognized that vitamin D₃ has immune-modulatory properties and that the variation in ultraviolet (UV) exposure affects vitamin D₃ status. Here, we investigated if and to what extent seasonality of vitamin D₃ levels are associated with changes in T cell numbers and phenotypes. Every three months during the course of the entire year, human PBMC and whole blood from 15 healthy subjects were sampled and analyzed using flow cytometry. We observed that elevated serum 25(OH)D₃ and 1,25(OH)(2)D₃ levels in summer were associated with a higher number of peripheral CD4+ and CD8+ T cells. In addition, an increase in naïve CD4+CD45RA+ T cells with a reciprocal drop in memory CD4+CD45RO+ T cells was observed. The increase in CD4+CD45RA+ T cell count was a result of heightened proliferative capacity rather than recent thymic emigration of T cells. The percentage of Treg dropped in summer, but not the absolute Treg numbers. Notably, in the Treg population, the levels of forkhead box protein 3 (Foxp3) expression were increased in summer. Skin, gut and lymphoid tissue homing potential was increased during summer as well, exemplified by increased CCR4, CCR6, CLA, CCR9 and CCR7 levels. Also, in summer, CD4+ and CD8+ T cells revealed a reduced capacity to produce pro-inflammatory cytokines. In conclusion, seasonal variation in vitamin D₃ status in vivo throughout the year is associated with changes in the human peripheral T cell compartment and may as such explain some of the seasonal variation in immune status which has been observed previously. Given that the current observations are limited to healthy adult males, larger population-based studies would be useful to validate these findings.
众所周知,维生素 D₃ 具有免疫调节特性,而紫外线(UV)暴露的变化会影响维生素 D₃ 状态。在这里,我们研究了维生素 D₃ 水平的季节性变化是否以及在何种程度上与 T 细胞数量和表型的变化相关。在整个研究期间,每三个月采集 15 名健康受试者的 PBMC 和全血样本,并使用流式细胞术进行分析。我们观察到,夏季血清 25(OH)D₃ 和 1,25(OH)(2)D₃ 水平升高与外周血 CD4+和 CD8+T 细胞数量增加有关。此外,我们还观察到,幼稚 CD4+CD45RA+T 细胞数量增加,而记忆 CD4+CD45RO+T 细胞数量减少。CD4+CD45RA+T 细胞计数的增加是由于细胞增殖能力增强,而不是 T 细胞近期从胸腺迁出。夏季 Treg 细胞的百分比下降,但绝对数量不变。值得注意的是,在 Treg 细胞群中,Foxp3 表达水平在夏季增加。夏季皮肤、肠道和淋巴组织归巢潜能也增加,表现为 CCR4、CCR6、CLA、CCR9 和 CCR7 水平升高。此外,在夏季,CD4+和 CD8+T 细胞产生促炎细胞因子的能力降低。总之,全年维生素 D₃ 状态的季节性变化与人类外周 T 细胞群的变化有关,这可能解释了之前观察到的一些免疫状态的季节性变化。鉴于目前的观察结果仅限于健康成年男性,更大规模的基于人群的研究将有助于验证这些发现。