Emergence of NK Cell Hyporesponsiveness after Two IL-15 Stimulation Cycles

The Journal of Immunology : Official Journal of the American Association of Immunologists
Marie FrutosoErwan Mortier

Abstract

IL-15 is a cytokine playing a crucial role in the function of immune cells, including NK and CD8 T cells. In this study, we demonstrated that in vivo, in mice, IL-15-prestimulated NK cells were no longer able to respond to a second cycle of IL-15 stimulation. This was illustrated by defects in cell maturation, proliferation, and activation, seemingly linked to the environment surrounding NK cells but not related to the presence of CD4 regulatory T cells, TGF-β, or IL-10. Moreover, NK cells from immunodeficient mice could respond to two cycles of IL-15 stimulation, whereas an adoptive transfer of CD44+CD8+ cells impaired their responsiveness to the second cycle. Conversely, in immunocompetent mice, NK cell responsiveness to a second IL-15 stimulation was restored by the depletion of CD8+ cells. These biological findings refine our understanding of the complex mode of action of NK cells in vivo, and they should be taken into consideration for IL-15-based therapy.

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Citations

Oct 28, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Afam A OkoyeLouis J Picker
Sep 25, 2019·International Journal of Molecular Sciences·Marie Frutoso, Erwan Mortier
Nov 19, 2020·Journal for Immunotherapy of Cancer·Piera Filomena FioreBruno Azzarone
Jun 7, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Bai LiuHing C Wong
Oct 2, 2021·The Journal of Clinical Investigation·Zachary J Bernstein, Jamie B Spangler

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