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NADH oxidase-dependent CD39 expression by CD8+ T cells modulates interferon gamma responses via generation of adenosine

Author

Listed:
  • Aiping Bai

    (Beth Israel Deaconess Medical Center, Harvard University)

  • Alan Moss

    (Beth Israel Deaconess Medical Center, Harvard University)

  • Sonja Rothweiler

    (Beth Israel Deaconess Medical Center, Harvard University)

  • Maria Serena Longhi

    (Beth Israel Deaconess Medical Center, Harvard University)

  • Yan Wu

    (Beth Israel Deaconess Medical Center, Harvard University)

  • Wolfgang G. Junger

    (Beth Israel Deaconess Medical Center, Harvard University)

  • Simon C. Robson

    (Beth Israel Deaconess Medical Center, Harvard University)

Abstract

Interferon gamma (IFNγ)-producing CD8+ T cells (Tc1) play important roles in immunological disease. We now report that CD3/CD28-mediated stimulation of CD8+ T cells to generate Tc1 cells, not only increases IFNγ production but also boosts the generation of reactive oxygen species (ROS) and augments expression of CD39. Inhibition of NADPH oxidases or knockdown of gp91phox in CD8+ T cells abrogates ROS generation, which in turn modulates JNK and NFκB signalling with decreases in both IFNγ levels and CD39 expression. CD39+CD8+ T cells substantially inhibit IFNγ production by CD39−CD8+ T cells via the paracrine generation of adenosine, which is operational via adenosine type 2A receptors. Increases in numbers of CD39+CD8+ T cells and associated enhancements in ROS signal transduction are noted in cells from patients with Crohn’s disease. Our findings provide insights into Tc1-mediated IFNγ responses and ROS generation and link these pathways to CD39/adenosine-mediated effects in immunological disease.

Suggested Citation

  • Aiping Bai & Alan Moss & Sonja Rothweiler & Maria Serena Longhi & Yan Wu & Wolfgang G. Junger & Simon C. Robson, 2015. "NADH oxidase-dependent CD39 expression by CD8+ T cells modulates interferon gamma responses via generation of adenosine," Nature Communications, Nature, vol. 6(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9819
    DOI: 10.1038/ncomms9819
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    1. Inna Starskaia & Milla Valta & Sami Pietilä & Tomi Suomi & Sirpa Pahkuri & Ubaid Ullah Kalim & Omid Rasool & Emilie Rydgren & Heikki Hyöty & Mikael Knip & Riitta Veijola & Jorma Ilonen & Jorma Toppari, 2024. "Distinct cellular immune responses in children en route to type 1 diabetes with different first-appearing autoantibodies," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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