IL-2-dependent tuning of NK cell sensitivity for target cells is controlled by regulatory T cells Journal Article
| Authors: | Gasteiger, G.; Hemmers, S.; Firth, M. A.; Floc'h, A. L.; Huse, M.; Sun, J. C.; Rudensky, A. Y. |
| Article 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 selfand 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. © 2013 Gasteiger et al. |
| Keywords: | controlled study; nonhuman; animal cell; mouse; phenotype; interleukin 2; animal experiment; cell lineage; regulatory t lymphocyte; cd4+ t lymphocyte; natural killer cell; cytokine production; target cell; autoimmunity; innate immunity; adaptive immunity; t cell depletion; cell adhesion; immunocompetent cell; natural killer cell mediated cytotoxicity |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 210 |
| Issue: | 6 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2013-06-03 |
| Start Page: | 1067 |
| End Page: | 1078 |
| Language: | English |
| DOI: | 10.1084/jem.20122462 |
| PROVIDER: | scopus |
| PMCID: | PMC3674692 |
| PUBMED: | 23650441 |
| DOI/URL: | |
| Notes: | --- - Cited By (since 1996):3 - "Export Date: 4 September 2013" - "CODEN: JEMEA" - "Source: Scopus" |
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