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Continuous engagement of a self-specific activation receptor induces NK cell tolerance

Natural killer (NK) cell tolerance mechanisms are incompletely understood. One possibility is that they possess self-specific activation receptors that result in hyporesponsiveness unless modulated by self–major histocompatability complex (MHC)–specific inhibitory receptors. As putative self-specifi...

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Autores principales: Tripathy, Sandeep K., Keyel, Peter A., Yang, Liping, Pingel, Jeanette T., Cheng, Tammy P., Schneeberger, Achim, Yokoyama, Wayne M.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2525593/
https://www.ncbi.nlm.nih.gov/pubmed/18606857
http://dx.doi.org/10.1084/jem.20072446
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author Tripathy, Sandeep K.
Keyel, Peter A.
Yang, Liping
Pingel, Jeanette T.
Cheng, Tammy P.
Schneeberger, Achim
Yokoyama, Wayne M.
author_facet Tripathy, Sandeep K.
Keyel, Peter A.
Yang, Liping
Pingel, Jeanette T.
Cheng, Tammy P.
Schneeberger, Achim
Yokoyama, Wayne M.
author_sort Tripathy, Sandeep K.
collection PubMed
description Natural killer (NK) cell tolerance mechanisms are incompletely understood. One possibility is that they possess self-specific activation receptors that result in hyporesponsiveness unless modulated by self–major histocompatability complex (MHC)–specific inhibitory receptors. As putative self-specific activation receptors have not been well characterized, we studied a transgenic C57BL/6 mouse that ubiquitously expresses m157 (m157-Tg), which is the murine cytomegalovirus (MCMV)–encoded ligand for the Ly49H NK cell activation receptor. The transgenic mice were more susceptible to MCMV infection and were unable to reject m157-Tg bone marrow, suggesting defects in Ly49H(+) NK cells. There was a reversible hyporesponsiveness of Ly49H(+) NK cells that extended to Ly49H-independent stimuli. Continuous Ly49H–m157 interaction was necessary for the functional defects. Interestingly, functional defects occurred when mature wild-type NK cells were adoptively transferred to m157-Tg mice, suggesting that mature NK cells may acquire hyporesponsiveness. Importantly, NK cell tolerance caused by Ly49H–m157 interaction was similar in NK cells regardless of expression of Ly49C, an inhibitory receptor specific for a self-MHC allele in C57BL/6 mice. Thus, engagement of self-specific activation receptors in vivo induces an NK cell tolerance effect that is not affected by self-MHC–specific inhibitory receptors.
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spelling pubmed-25255932009-02-04 Continuous engagement of a self-specific activation receptor induces NK cell tolerance Tripathy, Sandeep K. Keyel, Peter A. Yang, Liping Pingel, Jeanette T. Cheng, Tammy P. Schneeberger, Achim Yokoyama, Wayne M. J Exp Med Articles Natural killer (NK) cell tolerance mechanisms are incompletely understood. One possibility is that they possess self-specific activation receptors that result in hyporesponsiveness unless modulated by self–major histocompatability complex (MHC)–specific inhibitory receptors. As putative self-specific activation receptors have not been well characterized, we studied a transgenic C57BL/6 mouse that ubiquitously expresses m157 (m157-Tg), which is the murine cytomegalovirus (MCMV)–encoded ligand for the Ly49H NK cell activation receptor. The transgenic mice were more susceptible to MCMV infection and were unable to reject m157-Tg bone marrow, suggesting defects in Ly49H(+) NK cells. There was a reversible hyporesponsiveness of Ly49H(+) NK cells that extended to Ly49H-independent stimuli. Continuous Ly49H–m157 interaction was necessary for the functional defects. Interestingly, functional defects occurred when mature wild-type NK cells were adoptively transferred to m157-Tg mice, suggesting that mature NK cells may acquire hyporesponsiveness. Importantly, NK cell tolerance caused by Ly49H–m157 interaction was similar in NK cells regardless of expression of Ly49C, an inhibitory receptor specific for a self-MHC allele in C57BL/6 mice. Thus, engagement of self-specific activation receptors in vivo induces an NK cell tolerance effect that is not affected by self-MHC–specific inhibitory receptors. The Rockefeller University Press 2008-08-04 /pmc/articles/PMC2525593/ /pubmed/18606857 http://dx.doi.org/10.1084/jem.20072446 Text en © 2008 Tripathy et al. 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.jem.org/misc/terms.shtml). 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 Articles
Tripathy, Sandeep K.
Keyel, Peter A.
Yang, Liping
Pingel, Jeanette T.
Cheng, Tammy P.
Schneeberger, Achim
Yokoyama, Wayne M.
Continuous engagement of a self-specific activation receptor induces NK cell tolerance
title Continuous engagement of a self-specific activation receptor induces NK cell tolerance
title_full Continuous engagement of a self-specific activation receptor induces NK cell tolerance
title_fullStr Continuous engagement of a self-specific activation receptor induces NK cell tolerance
title_full_unstemmed Continuous engagement of a self-specific activation receptor induces NK cell tolerance
title_short Continuous engagement of a self-specific activation receptor induces NK cell tolerance
title_sort continuous engagement of a self-specific activation receptor induces nk cell tolerance
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2525593/
https://www.ncbi.nlm.nih.gov/pubmed/18606857
http://dx.doi.org/10.1084/jem.20072446
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