Differentially expressed potassium channels are associated with function of human effector memory CD8+ T cells

Ji Hyun Sim, Kyung Soo Kim, Hyoungjun Park, Kyung Jin Kim, Haiyue Lin, Tae Joo Kim, Hyun Mu Shin, Gwanghun Kim, Dong Sup Lee, Chan Wook Park, Dong Hun Lee, Insoo Kang, Sung Joon Kim, Chung Hyun Cho, Junsang Doh, Hang Rae Kim

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The voltage-gated potassium channel, Kv1.3, and the Ca2+-activated potassium channel, KCa3.1, regulate membrane potentials in T cells, thereby controlling T cell activation and cytokine production. However, little is known about the expression and function of potassium channels in human effector memory (EM) CD8+ T cells that can be further divided into functionally distinct subsets based on the expression of the interleukin (IL)-7 receptor alpha (IL-7Ra) chain. Herein, we investigated the functional expression and roles of Kv1.3 and KCa3.1 in EM CD8+ T cells that express high or low levels of the IL-7 receptor alpha chain (IL-7Rαhigh and IL-7Rαlow, respectively). In contrast to the significant activity of Kv1.3 and KCa3.1 in IL-7Rαhigh EM CD8+ T cells, IL-7Rαlow EM CD8+ T cells showed lower expression of Kv1.3 and insignificant expression of KCa3.1. Kv1.3 was involved in the modulation of cell proliferation and IL-2 production, whereas KCa3.1 affected the motility of EM CD8+ T cells. The lower motility of IL-7Rαlow EM CD8+ T cells was demonstrated using transendothelial migration and motility assays with intercellular adhesion molecule 1-and/or chemokine stromal cell-derived factor-1a-coated surfaces. Consistent with the lower migration property, IL-7Rαlow EM CD8+ T cells were found less frequently in human skin. Stimulating IL-7Rαlow EM CD8+ T cells with IL-2 or IL-15 increased their motility and recovery of KCa3.1 activity. Our findings demonstrate that Kv1.3 and KCa3.1 are differentially involved in the functions of EM CD8+ T cells. The weak expression of potassium channels in IL-7Rαlow EM CD8+ T cells can be revived by stimulation with IL-2 or IL-15, which restores the associated functions. This study suggests that IL-7Rαhigh EM CD8+ T cells with functional potassium channels may serve as a reservoir for effector CD8+T cells during peripheral inflammation.

Original languageEnglish
Article number859
JournalFrontiers in Immunology
Volume8
Issue numberJUL
DOIs
StatePublished - 24 Jul 2017

Keywords

  • Calcium-activated potassium channel KCa3.1
  • Human effector memory CD8 T cells
  • Interleukin-7Rα effector memory CD8 T cells
  • T-cell motility
  • Transendothelial migration
  • Voltage-gated potassium channel Kv1.3

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