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Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice
Reactivation of human cytomegalovirus (HCMV) can cause severe disease in recipients of hematopoietic stem cell transplantation. Although preclinical research in murine models as well as clinical trials have provided 'proof of concept' for infection control by pre-emptive CD8 T-cell immunot...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504510/ https://www.ncbi.nlm.nih.gov/pubmed/26181057 http://dx.doi.org/10.1371/journal.ppat.1005049 |
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author | Thomas, Simone Klobuch, Sebastian Podlech, Jürgen Plachter, Bodo Hoffmann, Petra Renzaho, Angelique Theobald, Matthias Reddehase, Matthias J. Herr, Wolfgang Lemmermann, Niels A. W. |
author_facet | Thomas, Simone Klobuch, Sebastian Podlech, Jürgen Plachter, Bodo Hoffmann, Petra Renzaho, Angelique Theobald, Matthias Reddehase, Matthias J. Herr, Wolfgang Lemmermann, Niels A. W. |
author_sort | Thomas, Simone |
collection | PubMed |
description | Reactivation of human cytomegalovirus (HCMV) can cause severe disease in recipients of hematopoietic stem cell transplantation. Although preclinical research in murine models as well as clinical trials have provided 'proof of concept' for infection control by pre-emptive CD8 T-cell immunotherapy, there exists no predictive model to experimentally evaluate parameters that determine antiviral efficacy of human T cells in terms of virus control in functional organs, prevention of organ disease, and host survival benefit. We here introduce a novel mouse model for testing HCMV epitope-specific human T cells. The HCMV UL83/pp65-derived NLV-peptide was presented by transgenic HLA-A2.1 in the context of a lethal infection of NOD/SCID/IL-2rg(-/-) mice with a chimeric murine CMV, mCMV-NLV. Scenarios of HCMV-seropositive and -seronegative human T-cell donors were modeled by testing peptide-restimulated and T-cell receptor-transduced human T cells, respectively. Upon transfer, the T cells infiltrated host tissues in an epitope-specific manner, confining the infection to nodular inflammatory foci. This resulted in a significant reduction of viral load, diminished organ pathology, and prolonged survival. The model has thus proven its potential for a preclinical testing of the protective antiviral efficacy of HCMV epitope-specific human T cells in the evaluation of new approaches to an immunotherapy of CMV disease. |
format | Online Article Text |
id | pubmed-4504510 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45045102015-07-17 Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice Thomas, Simone Klobuch, Sebastian Podlech, Jürgen Plachter, Bodo Hoffmann, Petra Renzaho, Angelique Theobald, Matthias Reddehase, Matthias J. Herr, Wolfgang Lemmermann, Niels A. W. PLoS Pathog Research Article Reactivation of human cytomegalovirus (HCMV) can cause severe disease in recipients of hematopoietic stem cell transplantation. Although preclinical research in murine models as well as clinical trials have provided 'proof of concept' for infection control by pre-emptive CD8 T-cell immunotherapy, there exists no predictive model to experimentally evaluate parameters that determine antiviral efficacy of human T cells in terms of virus control in functional organs, prevention of organ disease, and host survival benefit. We here introduce a novel mouse model for testing HCMV epitope-specific human T cells. The HCMV UL83/pp65-derived NLV-peptide was presented by transgenic HLA-A2.1 in the context of a lethal infection of NOD/SCID/IL-2rg(-/-) mice with a chimeric murine CMV, mCMV-NLV. Scenarios of HCMV-seropositive and -seronegative human T-cell donors were modeled by testing peptide-restimulated and T-cell receptor-transduced human T cells, respectively. Upon transfer, the T cells infiltrated host tissues in an epitope-specific manner, confining the infection to nodular inflammatory foci. This resulted in a significant reduction of viral load, diminished organ pathology, and prolonged survival. The model has thus proven its potential for a preclinical testing of the protective antiviral efficacy of HCMV epitope-specific human T cells in the evaluation of new approaches to an immunotherapy of CMV disease. Public Library of Science 2015-07-16 /pmc/articles/PMC4504510/ /pubmed/26181057 http://dx.doi.org/10.1371/journal.ppat.1005049 Text en © 2015 Thomas 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Thomas, Simone Klobuch, Sebastian Podlech, Jürgen Plachter, Bodo Hoffmann, Petra Renzaho, Angelique Theobald, Matthias Reddehase, Matthias J. Herr, Wolfgang Lemmermann, Niels A. W. Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice |
title | Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice |
title_full | Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice |
title_fullStr | Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice |
title_full_unstemmed | Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice |
title_short | Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice |
title_sort | evaluating human t-cell therapy of cytomegalovirus organ disease in hla-transgenic mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4504510/ https://www.ncbi.nlm.nih.gov/pubmed/26181057 http://dx.doi.org/10.1371/journal.ppat.1005049 |
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