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

Marie Frutoso 1 Sébastien Morisseau 1 Fella Tamzalit 1 Agnès Quéméner 1 Dihia Meghnem 1 Isabelle Leray 1 yannick Jacques 1 Erwan Mortier 1, * 
* Corresponding author
1 CRCINA-ÉQUIPE 1 - Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications
CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers
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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Submitted on : Friday, June 1, 2018 - 2:59:10 PM
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Marie Frutoso, Sébastien Morisseau, Fella Tamzalit, Agnès Quéméner, Dihia Meghnem, et al.. Emergence of NK Cell Hyporesponsiveness after Two IL-15 Stimulation Cycles. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2018, Epub ahead of print. ⟨10.4049/jimmunol.1800086⟩. ⟨inserm-01805185⟩



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