First Department of Pediatrics, Semmelweis University, Budapest, Hungary.
Immunobiology. 2013 Mar;218(3):311-6. doi: 10.1016/j.imbio.2012.05.013. Epub 2012 May 23.
The transient increase of the cytoplasmic free calcium level plays a key role in the process of lymphocyte activation. Kv1.3 and IKCa1 potassium channels are important regulators of the maintenance of calcium influx during lymphocyte activation and present a possible target for selective immunomodulation.
Case-control study.
We took peripheral blood samples from 10 healthy individuals and 9 recently diagnosed rheumatoid arthritis (RA) patients receiving no anti-rheumatic treatment. We evaluated calcium influx kinetics following activation in CD4, Th1, Th2 and CD8 cells applying a novel flow cytometry approach. We also assessed the sensitivity of the above subsets to specific inhibition of the Kv1.3 and IKCa1 potassium channels.
The peak of calcium influx in lymphocytes isolated from RA patients is reached more rapidly, indicating that they respond more quickly to stimulation compared to controls. In healthy individuals, the inhibition of the IKCa1 channel decreased calcium influx in Th2 and CD4 cells to a lower extent than in Th1 and CD8 cells. On the contrary, the inhibition of Kv1.3 channels resulted in a larger decrease of calcium entry in Th2 and CD4 than in Th1 and CD8 cells. No difference was detected between Th1 and Th2 or CD4 and CD8 cells in the sensitivity to IKCa1 channel inhibition among lymphocytes of RA patients. However, specific inhibition of the Kv1.3 channel acts differentially on calcium influx kinetics in RA lymphocyte subsets. Th2 and particularly CD8 cells are inhibited more dominantly than Th1 and CD4 cells.
The inhibition of Kv1.3 channels does not seem to be specific enough in peripheral RA lymphocytes, since anti-inflammatory Th2 cells are also affected to a noteworthy extent.
细胞质游离钙水平的短暂增加在淋巴细胞激活过程中起着关键作用。Kv1.3 和 IKCa1 钾通道是维持淋巴细胞激活过程中钙内流的重要调节剂，是选择性免疫调节的一个可能靶点。
病例对照研究。
我们从 10 名健康个体和 9 名正在接受类风湿关节炎（RA）治疗的新诊断 RA 患者中采集外周血样本。我们应用一种新的流式细胞术方法评估 CD4、Th1、Th2 和 CD8 细胞激活后钙内流动力学。我们还评估了上述亚群对 Kv1.3 和 IKCa1 钾通道特异性抑制的敏感性。
与对照组相比，来自 RA 患者的淋巴细胞钙内流峰值出现得更快，这表明它们对刺激的反应更快。在健康个体中，IKCa1 通道的抑制使 Th2 和 CD4 细胞的钙内流减少的程度低于 Th1 和 CD8 细胞。相反，Kv1.3 通道的抑制导致 Th2 和 CD4 细胞的钙内流减少幅度大于 Th1 和 CD8 细胞。在 RA 患者的淋巴细胞中，我们未发现 Th1 和 Th2 或 CD4 和 CD8 细胞之间对 IKCa1 通道抑制的敏感性存在差异。然而，Kv1.3 通道的特异性抑制对 RA 淋巴细胞亚群的钙内流动力学有不同的作用。Th2 细胞，特别是 CD8 细胞比 Th1 和 CD4 细胞受到更显著的抑制。
Kv1.3 通道的抑制在 RA 外周淋巴细胞中似乎不够特异，因为抗炎性 Th2 细胞也受到相当程度的影响。
