IL-2-dependent tuning of NK cell sensitivity for target cells is controlled by regulatory T cells.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Gasteiger, G; Hemmers, S; Firth, MA; Le Floc'h, A; Huse, M; Sun, JC; Rudensky, AY

Published Date

  • June 3, 2013

Published In

Volume / Issue

  • 210 / 6

Start / End Page

  • 1167 - 1178

PubMed ID

  • 23650441

Pubmed Central ID

  • PMC3674692

Electronic International Standard Serial Number (EISSN)

  • 1540-9538

Digital Object Identifier (DOI)

  • 10.1084/jem.20122462

Language

  • eng

Conference Location

  • United States