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Differentially Expressed Potassium Channels Are Associated with Function of Human Effector Memory CD8+ T Cells
Ji Hyun Sim1, Kyung Soo Kim2,3, Hyoungjun Park4
1Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul, South Korea.
Frontiers in Immunology
|August 10, 2017
Summary
Voltage-gated potassium channel Kv1.3 and Ca2+-activated channel KCa3.1 expression differs between human effector memory CD8+ T cell subsets. IL-7Rαlow cells show reduced channel activity, impacting proliferation and motility, but can be restored by IL-2 or IL-15.
Area of Science:
- Immunology
- Cell Biology
- Ion Channel Physiology
Background:
- T cell activation, proliferation, and cytokine production are regulated by membrane potential, influenced by potassium channels like Kv1.3 and KCa3.1.
- Human effector memory (EM) CD8+ T cells comprise subsets with distinct functions, partly defined by interleukin-7 receptor alpha (IL-7Rα) expression levels.
- The specific roles and expression patterns of Kv1.3 and KCa3.1 in IL-7Rα-defined EM CD8+ T cell subsets remain largely uncharacterized.
Purpose of the Study:
- To investigate the functional expression of Kv1.3 and KCa3.1 in human EM CD8+ T cells with high (IL-7Rαhigh) or low (IL-7Rαlow) IL-7Rα expression.
- To determine the specific roles of Kv1.3 and KCa3.1 in the functions of these distinct EM CD8+ T cell subsets.
- To explore potential mechanisms for modulating the function of IL-7Rαlow EM CD8+ T cells.
Main Methods:
- Flow cytometry to assess IL-7Rα expression on EM CD8+ T cells.
- Patch-clamp electrophysiology to measure Kv1.3 and KCa3.1 channel activity.
- Cell proliferation assays and cytokine production measurements (e.g., IL-2).
- Transendothelial migration and motility assays using specific surface coatings (ICAM-1, SDF-1α).
- In vitro stimulation of T cells with cytokines (IL-2, IL-15).
Main Results:
- IL-7Rαhigh EM CD8+ T cells exhibited significant Kv1.3 and KCa3.1 activity, whereas IL-7Rαlow cells showed reduced Kv1.3 and minimal KCa3.1 expression.
- Kv1.3 activity was linked to T cell proliferation and IL-2 production, while KCa3.1 regulated T cell motility.
- IL-7Rαlow EM CD8+ T cells displayed lower motility and transendothelial migration, correlating with their reduced presence in human skin.
- Stimulation with IL-2 or IL-15 enhanced the motility of IL-7Rαlow EM CD8+ T cells and restored KCa3.1 activity.
Conclusions:
- Kv1.3 and KCa3.1 play differential roles in the function of human EM CD8+ T cell subsets.
- The diminished function of IL-7Rαlow EM CD8+ T cells, characterized by low potassium channel activity, can be reversed by IL-2 or IL-15 stimulation.
- IL-7Rαhigh EM CD8+ T cells with active potassium channels may represent a crucial reservoir of effector T cells during peripheral inflammation.
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