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Tracking the fate of antigen-specific versus cytokine-activated natural killer cells after cytomegalovirus infection
Natural killer (NK) cells provide important host defense and can generate long-lived memory NK cells. Here, by using novel transgenic mice carrying inducible Cre expressed under the control of Ncr1 gene, we demonstrated that two distinct long-lived NK cell subsets differentiate in a mouse model of c...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5110025/ https://www.ncbi.nlm.nih.gov/pubmed/27810928 http://dx.doi.org/10.1084/jem.20160726 |
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author | Nabekura, Tsukasa Lanier, Lewis L. |
author_facet | Nabekura, Tsukasa Lanier, Lewis L. |
author_sort | Nabekura, Tsukasa |
collection | PubMed |
description | Natural killer (NK) cells provide important host defense and can generate long-lived memory NK cells. Here, by using novel transgenic mice carrying inducible Cre expressed under the control of Ncr1 gene, we demonstrated that two distinct long-lived NK cell subsets differentiate in a mouse model of cytomegalovirus (MCMV) infection. NK cells expressing the MCMV-specific Ly49H receptor differentiated into memory NK cells by an activating signaling through Ly49H and Ly49H(−) NK cells differentiated into cytokine-activated NK cells by exposure to inflammatory cytokines during infection. Interleukin-12 is indispensable for optimal generation of both antigen-specific memory NK cells and cytokine-activated NK cells. MCMV-specific memory NK cells show enhanced effector function and augmented antitumor activity in vivo as compared with cytokine-activated NK cells, whereas cytokine-activated NK cells exhibited a more robust response to IL-15 and persisted better in an MCMV-free environment. These findings reveal that NK cells are capable of differentiation into distinct long-lived subsets with different functional properties. |
format | Online Article Text |
id | pubmed-5110025 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-51100252017-05-14 Tracking the fate of antigen-specific versus cytokine-activated natural killer cells after cytomegalovirus infection Nabekura, Tsukasa Lanier, Lewis L. J Exp Med Research Articles Natural killer (NK) cells provide important host defense and can generate long-lived memory NK cells. Here, by using novel transgenic mice carrying inducible Cre expressed under the control of Ncr1 gene, we demonstrated that two distinct long-lived NK cell subsets differentiate in a mouse model of cytomegalovirus (MCMV) infection. NK cells expressing the MCMV-specific Ly49H receptor differentiated into memory NK cells by an activating signaling through Ly49H and Ly49H(−) NK cells differentiated into cytokine-activated NK cells by exposure to inflammatory cytokines during infection. Interleukin-12 is indispensable for optimal generation of both antigen-specific memory NK cells and cytokine-activated NK cells. MCMV-specific memory NK cells show enhanced effector function and augmented antitumor activity in vivo as compared with cytokine-activated NK cells, whereas cytokine-activated NK cells exhibited a more robust response to IL-15 and persisted better in an MCMV-free environment. These findings reveal that NK cells are capable of differentiation into distinct long-lived subsets with different functional properties. The Rockefeller University Press 2016-11-14 /pmc/articles/PMC5110025/ /pubmed/27810928 http://dx.doi.org/10.1084/jem.20160726 Text en © 2016 Nabekura and Lanier This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Nabekura, Tsukasa Lanier, Lewis L. Tracking the fate of antigen-specific versus cytokine-activated natural killer cells after cytomegalovirus infection |
title | Tracking the fate of antigen-specific versus cytokine-activated natural killer cells after cytomegalovirus infection |
title_full | Tracking the fate of antigen-specific versus cytokine-activated natural killer cells after cytomegalovirus infection |
title_fullStr | Tracking the fate of antigen-specific versus cytokine-activated natural killer cells after cytomegalovirus infection |
title_full_unstemmed | Tracking the fate of antigen-specific versus cytokine-activated natural killer cells after cytomegalovirus infection |
title_short | Tracking the fate of antigen-specific versus cytokine-activated natural killer cells after cytomegalovirus infection |
title_sort | tracking the fate of antigen-specific versus cytokine-activated natural killer cells after cytomegalovirus infection |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5110025/ https://www.ncbi.nlm.nih.gov/pubmed/27810928 http://dx.doi.org/10.1084/jem.20160726 |
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