IL-2-dependent tuning of NK cell sensitivity for target cells is controlled by regulatory T cells.
AuthorGasteiger, G; Hemmers, S; Firth, MA; Le Floc'h, A; Huse, M; Sun, JC; Rudensky, AY
Source TitleJournal of Experimental Medicine
PublisherRockefeller University Press
University of Melbourne Author/sFirth, Matthew
AffiliationMedical Biology (W.E.H.I.)
Document TypeJournal Article
CitationsGasteiger, G., Hemmers, S., Firth, M. A., Le Floc'h, A., Huse, M., Sun, J. C. & Rudensky, A. Y. (2013). IL-2-dependent tuning of NK cell sensitivity for target cells is controlled by regulatory T cells.. J Exp Med, 210 (6), pp.1167-1178. https://doi.org/10.1084/jem.20122462.
Access StatusOpen Access
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674692
The emergence of the adaptive immune system took a toll in the form of pathologies mediated by self-reactive cells. Regulatory T cells (T reg cells) exert a critical brake on responses of T and B lymphocytes to self- and foreign antigens. Here, we asked whether T reg cells are required to restrain NK cells, the third lymphocyte lineage, whose features combine innate and adaptive immune cell properties. Although depletion of T reg cells led to systemic fatal autoimmunity, NK cell tolerance and reactivity to strong activating self- and non-self-ligands remained largely intact. In contrast, missing-self responses were increased in the absence of T reg cells as the result of heightened IL-2 availability. We found that IL-2 rapidly boosted the capacity of NK cells to productively engage target cells and enabled NK cell responses to weak stimulation. Our results suggest that IL-2-dependent adaptive-innate lymphocyte cross talk tunes NK cell reactivity and that T reg cells restrain NK cell cytotoxicity by limiting the availability of IL-2.
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