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Potassium channels Kv1.3 and KCa3.1 cooperatively and compensatorily regulate antigen-specific memory T cell functions

Author

Listed:
  • Eugene Y. Chiang

    (Genentech Inc.)

  • Tianbo Li

    (Genentech Inc.)

  • Surinder Jeet

    (Genentech Inc.)

  • Ivan Peng

    (Genentech Inc.)

  • Juan Zhang

    (Genentech Inc.)

  • Wyne P. Lee

    (Genentech Inc.)

  • Jason DeVoss

    (Genentech Inc.)

  • Patrick Caplazi

    (Genentech Inc.)

  • Jun Chen

    (Genentech Inc.)

  • Søren Warming

    (Genentech Inc.)

  • David H. Hackos

    (Genentech Inc.)

  • Susmith Mukund

    (Genentech Inc.)

  • Christopher M. Koth

    (Genentech Inc.)

  • Jane L. Grogan

    (Genentech Inc.)

Abstract

Voltage-gated Kv1.3 and Ca2+-dependent KCa3.1 are the most prevalent K+ channels expressed by human and rat T cells. Despite the preferential upregulation of Kv1.3 over KCa3.1 on autoantigen-experienced effector memory T cells, whether Kv1.3 is required for their induction and function is unclear. Here we show, using Kv1.3-deficient rats, that Kv1.3 is involved in the development of chronically activated antigen-specific T cells. Several immune responses are normal in Kv1.3 knockout (KO) rats, suggesting that KCa3.1 can compensate for the absence of Kv1.3 under these specific settings. However, experiments with Kv1.3 KO rats and Kv1.3 siRNA knockdown or channel-specific inhibition of human T cells show that maximal T-cell responses against autoantigen or repeated tetanus toxoid stimulations require both Kv1.3 and KCa3.1. Finally, our data also suggest that T-cell dependency on Kv1.3 or KCa3.1 might be irreversibly modulated by antigen exposure.

Suggested Citation

  • Eugene Y. Chiang & Tianbo Li & Surinder Jeet & Ivan Peng & Juan Zhang & Wyne P. Lee & Jason DeVoss & Patrick Caplazi & Jun Chen & Søren Warming & David H. Hackos & Susmith Mukund & Christopher M. Koth, 2017. "Potassium channels Kv1.3 and KCa3.1 cooperatively and compensatorily regulate antigen-specific memory T cell functions," Nature Communications, Nature, vol. 8(1), pages 1-16, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14644
    DOI: 10.1038/ncomms14644
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    Cited by:

    1. Heran Zhang & Ian R. Monk & Jessica Braverman & Claerwen M. Jones & Andrew G. Brooks & Timothy P. Stinear & Linda M. Wakim, 2024. "Staphylococcal superantigens evoke temporary and reversible T cell anergy, but fail to block the development of a bacterium specific cellular immune response," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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