Format

Send to

Choose Destination
Front Immunol. 2017 Jul 24;8:859. doi: 10.3389/fimmu.2017.00859. eCollection 2017.

Differentially Expressed Potassium Channels Are Associated with Function of Human Effector Memory CD8+ T Cells.

Sim JH1, Kim KS2,3, Park H4, Kim KJ2,5, Lin H2,3, Kim TJ1,2, Shin HM1,2,6,7, Kim G1,2,6, Lee DS1,2,6, Park CW8, Lee DH9, Kang I10, Kim SJ2,3,6,7, Cho CH2,5,6,7, Doh J4, Kim HR1,2,6,7.

Author information

1
Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul, South Korea.
2
Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.
3
Department of Physiology, Seoul National University College of Medicine, Seoul, South Korea.
4
Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang, South Korea.
5
Department of Pharmacology, Seoul National University College of Medicine, Seoul, South Korea.
6
BK21Plus Biomedical Science Project, Seoul National University College of Medicine, Seoul, South Korea.
7
Medical Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
8
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, South Korea.
9
Department of Dermatology, Seoul National University College of Medicine, Seoul, South Korea.
10
Department of Internal Medicine, Section of Rheumatology, Yale University School of Medicine, New Haven, CT, United States.

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-7Rα) 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-1α-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.

KEYWORDS:

T-cell motility; calcium-activated potassium channel KCa3.1; human effector memory CD8+ T cells; interleukin-7Rαlow effector memory CD8+ T cells; transendothelial migration; voltage-gated potassium channel Kv1.3

Supplemental Content

Full text links

Icon for Frontiers Media SA Icon for PubMed Central
Loading ...
Support Center