Modulation of Kv channel expression and function by TCR and costimulatory signals during peripheral CD4(+) lymphocyte differentiation.
Modulation of Kv channel expression and function by TCR and costimulatory signals during peripheral CD4(+) lymphocyte differentiation.
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DOI：
10.1084/jem.20020381
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发表时间：
2002-10-07
影响因子：
15.3
通讯作者：
Freedman, Bruce D
中科院分区：
文献类型：
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作者：
Liu, Qing-Hua;Fleischmann, Bernd K;Hondowicz, Brian;Maier, Curtis C;Turka, Laurence A;Yui, Katsuyuki;Kotlikoff, Michael I;Wells, Andrew D;Freedman, Bruce D
包括电压依赖性钾（Kv）通道在内的离子信号传导途径在外周T细胞的抗原介导的应答中起作用。然而，Kv通道如何与参与T细胞活化和分化的其他信号通路合作尚不清楚。我们报告说，多个KV通道表达幼稚的CD 4+淋巴细胞，和电流的幅度和动力学的抗原受体介导的刺激和共刺激信号调制。幼稚CD 4+淋巴细胞中表达的电流与Kv1.1、Kv1.2、Kv1.3和Kv1.6一致。由最佳TCR和共刺激产生的效应CD 4+细胞仅表现出Kv1.3电流，但水平比初始细胞高约6倍。通过部分刺激而失去能量的CD 4+淋巴细胞表现出类似的Kv1.1、Kv1.2和/或Kv1.6电流，但Kv1.3电流比初始细胞高出约三倍。为了确定Kv通道是否有助于幼稚T细胞、效应T细胞和无反应T细胞的不同功能，我们测试了它们在免疫调节细胞因子产生中的作用。每个Kv通道都是幼稚CD 4+淋巴细胞产生最大IL-2所必需的，而似乎没有一个通道在效应细胞产生IL-2、IL-4或IFN-γ中起作用。有趣的是，在无能量的淋巴细胞中的Kv通道主动抑制IL-4的产生，并且这些功能与调节膜电位和钙信号传导的作用一致。
Ionic signaling pathways, including voltage-dependent potassium (Kv) channels, are instrumental in antigen-mediated responses of peripheral T cells. However, how Kv channels cooperate with other signaling pathways involved in T cell activation and differentiation is unknown. We report that multiple Kv channels are expressed by naive CD4+ lymphocytes, and that the current amplitude and kinetics are modulated by antigen receptor–mediated stimulation and costimulatory signals. Currents expressed in naive CD4+ lymphocytes are consistent with Kv1.1, Kv1.2, Kv1.3, and Kv1.6. Effector CD4+ cells generated by optimal TCR and costimulation exhibit only Kv1.3 current, but at approximately sixfold higher levels than naive cells. CD4+ lymphocytes anergized through partial stimulation exhibit similar Kv1.1, Kv1.2, and/or Kv1.6 currents, but approximately threefold more Kv1.3 current than naive cells. To determine if Kv channels contribute to the distinct functions of naive, effector, and anergized T cells, we tested their role in immunoregulatory cytokine production. Each Kv channel is required for maximal IL-2 production by naive CD4+ lymphocytes, whereas none appears to play a role in IL-2, IL-4, or IFN-γ production by effector cells. Interestingly, Kv channels in anergized lymphocytes actively suppress IL-4 production, and these functions are consistent with a role in regulating the membrane potential and calcium signaling.