title: IL-2-dependent tuning of NK cell sensitivity for target cells is controlled by regulatory T cells.
abstract: 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.
authors: Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors: Georg
authors: G
authors: Gasteiger
authors: Saskia
authors: S
authors: Hemmers
authors: Matthew A
authors: MA
authors: Firth
authors: Audrey
authors: A
authors: Le Floc'h
authors: Morgan
authors: M
authors: Huse
authors: Joseph C
authors: JC
authors: Sun
authors: Alexander Y
authors: AY
authors: Rudensky
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D007108:Immune Tolerance / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D007376:Interleukin-2
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