Kollár Szonja, Berta László, Vásárhelyi Zsófia Eszter, Balog Attila, Vásárhelyi Barna, Rigó János, Toldi Gergely
Second Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary.
First Department of Pediatrics, Semmelweis University, Budapest, Hungary.
Oncotarget. 2015 May 30;6(15):13750-6. doi: 10.18632/oncotarget.3808.
Adaptive immunity and T cell function are affected by aging. Calcium influx patterns, regulated by Kv1.3 and IKCa1 potassium channels, influence T cell activation. We aimed to compare calcium influx kinetics in CD8, Th1 and Th2 cells in human peripheral blood samples obtained from five different age groups (cord blood, 10-15 ys, 25-40 ys, 45-55 ys, 60-75 ys).We measured calcium influx using flow cytometry in samples treated with or without specific inhibitors of Kv1.3 and IKCa1 channels (MGTX and TRAM, respectively).Calcium influx was higher in Th1 cells of adults, however, its extent decreased again with aging. Importantly, these changes were not detected in Th2 cells, where the pattern of calcium influx kinetics is similar throughout all investigated age groups. MGTX had a more pronounced inhibitory effect on calcium influx in Th2 cells, while in Th1 cells the same was true for TRAM in the 25-40 ys and 45-55 ys groups. Calcium influx of CD8 cells were inhibited to a similar extent by both applied inhibitors in these groups, and had no effect in the elderly.Altered lymphocyte potassium channel inhibitory patterns, regulators of calcium influx kinetics, might contribute to the development of age-related changes of T cell function.
适应性免疫和T细胞功能会受到衰老的影响。由Kv1.3和IKCa1钾通道调节的钙内流模式会影响T细胞的激活。我们旨在比较从五个不同年龄组(脐带血、10 - 15岁、25 - 40岁、45 - 55岁、60 - 75岁)获取的人类外周血样本中CD8细胞、Th1细胞和Th2细胞的钙内流动力学。我们使用流式细胞术在分别用Kv1.3和IKCa1通道的特异性抑制剂(分别为MGTX和TRAM)处理或未处理的样本中测量钙内流。成年人Th1细胞中的钙内流较高,然而,其程度会随着衰老再次降低。重要的是,在Th2细胞中未检测到这些变化,在所有研究的年龄组中,Th2细胞的钙内流动力学模式相似。MGTX对Th2细胞中的钙内流具有更显著的抑制作用,而在25 - 40岁和45 - 55岁组的Th1细胞中,TRAM对钙内流的抑制作用相同。在这些组中,两种应用的抑制剂对CD8细胞钙内流的抑制程度相似,而对老年人则没有影响。淋巴细胞钾通道抑制模式的改变,即钙内流动力学的调节因子,可能有助于T细胞功能与年龄相关变化的发展。