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NK cells negatively regulate CD8 T cells via natural cytotoxicity receptor (NCR) 1 during LCMV infection

Besides their function in recognizing cancerous and virally infected cells, natural killer (NK) cells have the potential to shape adaptive immune responses. However, the mechanisms employed by NK cells to negatively regulate virus-specific CD8 T cell responses remain to be fully defined. Using activ...

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Autores principales: Pallmer, Katharina, Barnstorf, Isabel, Baumann, Nicolas S., Borsa, Mariana, Jonjic, Stipan, Oxenius, Annette
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469806/
https://www.ncbi.nlm.nih.gov/pubmed/30995287
http://dx.doi.org/10.1371/journal.ppat.1007725
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author Pallmer, Katharina
Barnstorf, Isabel
Baumann, Nicolas S.
Borsa, Mariana
Jonjic, Stipan
Oxenius, Annette
author_facet Pallmer, Katharina
Barnstorf, Isabel
Baumann, Nicolas S.
Borsa, Mariana
Jonjic, Stipan
Oxenius, Annette
author_sort Pallmer, Katharina
collection PubMed
description Besides their function in recognizing cancerous and virally infected cells, natural killer (NK) cells have the potential to shape adaptive immune responses. However, the mechanisms employed by NK cells to negatively regulate virus-specific CD8 T cell responses remain to be fully defined. Using activating receptor natural cytotoxicity receptor (NCR) 1 deficient (NCR1(gfp/gfp)) mice, we found increased numbers of virus-specific CD8 T cells, leading to enhanced virus control during acute LCMV infection. Furthermore, virus-specific CD8 T cells were more activated in the absence of NCR1, resulting in exacerbated immunopathology, documented by weight loss, and superior virus control early during chronic LCMV infection. Transfer experiments of virus-specific CD8 T cells into NCR1 deficient hosts revealed a direct cross talk between NK and CD8 T cells. Studies on the splenic microarchitecture revealed pronounced disorganization of T cells in infected NCR1(gfp/gfp) mice, resulting in enhanced immunopathology and disruption of the T cell niche upon chronic LCMV infection. Our data show a novel pathway employed by NK cells to regulate antiviral CD8 T cell responses, namely direct recognition and elimination of activated CD8 T cells via NCR1 early during infection to protect the host from an overshooting T cell response.
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spelling pubmed-64698062019-05-03 NK cells negatively regulate CD8 T cells via natural cytotoxicity receptor (NCR) 1 during LCMV infection Pallmer, Katharina Barnstorf, Isabel Baumann, Nicolas S. Borsa, Mariana Jonjic, Stipan Oxenius, Annette PLoS Pathog Research Article Besides their function in recognizing cancerous and virally infected cells, natural killer (NK) cells have the potential to shape adaptive immune responses. However, the mechanisms employed by NK cells to negatively regulate virus-specific CD8 T cell responses remain to be fully defined. Using activating receptor natural cytotoxicity receptor (NCR) 1 deficient (NCR1(gfp/gfp)) mice, we found increased numbers of virus-specific CD8 T cells, leading to enhanced virus control during acute LCMV infection. Furthermore, virus-specific CD8 T cells were more activated in the absence of NCR1, resulting in exacerbated immunopathology, documented by weight loss, and superior virus control early during chronic LCMV infection. Transfer experiments of virus-specific CD8 T cells into NCR1 deficient hosts revealed a direct cross talk between NK and CD8 T cells. Studies on the splenic microarchitecture revealed pronounced disorganization of T cells in infected NCR1(gfp/gfp) mice, resulting in enhanced immunopathology and disruption of the T cell niche upon chronic LCMV infection. Our data show a novel pathway employed by NK cells to regulate antiviral CD8 T cell responses, namely direct recognition and elimination of activated CD8 T cells via NCR1 early during infection to protect the host from an overshooting T cell response. Public Library of Science 2019-04-17 /pmc/articles/PMC6469806/ /pubmed/30995287 http://dx.doi.org/10.1371/journal.ppat.1007725 Text en © 2019 Pallmer et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Pallmer, Katharina
Barnstorf, Isabel
Baumann, Nicolas S.
Borsa, Mariana
Jonjic, Stipan
Oxenius, Annette
NK cells negatively regulate CD8 T cells via natural cytotoxicity receptor (NCR) 1 during LCMV infection
title NK cells negatively regulate CD8 T cells via natural cytotoxicity receptor (NCR) 1 during LCMV infection
title_full NK cells negatively regulate CD8 T cells via natural cytotoxicity receptor (NCR) 1 during LCMV infection
title_fullStr NK cells negatively regulate CD8 T cells via natural cytotoxicity receptor (NCR) 1 during LCMV infection
title_full_unstemmed NK cells negatively regulate CD8 T cells via natural cytotoxicity receptor (NCR) 1 during LCMV infection
title_short NK cells negatively regulate CD8 T cells via natural cytotoxicity receptor (NCR) 1 during LCMV infection
title_sort nk cells negatively regulate cd8 t cells via natural cytotoxicity receptor (ncr) 1 during lcmv infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469806/
https://www.ncbi.nlm.nih.gov/pubmed/30995287
http://dx.doi.org/10.1371/journal.ppat.1007725
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