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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-07-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC4504510?pdf=render |
| _version_ | 1818176146143969280 |
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| author | Simone Thomas Sebastian Klobuch Jürgen Podlech Bodo Plachter Petra Hoffmann Angelique Renzaho Matthias Theobald Matthias J Reddehase Wolfgang Herr Niels A W Lemmermann |
| author_facet | Simone Thomas Sebastian Klobuch Jürgen Podlech Bodo Plachter Petra Hoffmann Angelique Renzaho Matthias Theobald Matthias J Reddehase Wolfgang Herr Niels A W Lemmermann |
| author_sort | Simone Thomas |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-11T20:11:33Z |
| format | Article |
| id | doaj.art-579f514b4d28474c89dfe2d10ed17aa1 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-11T20:11:33Z |
| publishDate | 2015-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-579f514b4d28474c89dfe2d10ed17aa12022-12-22T00:52:17ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742015-07-01117e100504910.1371/journal.ppat.1005049Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice.Simone ThomasSebastian KlobuchJürgen PodlechBodo PlachterPetra HoffmannAngelique RenzahoMatthias TheobaldMatthias J ReddehaseWolfgang HerrNiels A W LemmermannReactivation 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.http://europepmc.org/articles/PMC4504510?pdf=render |
| spellingShingle | Simone Thomas Sebastian Klobuch Jürgen Podlech Bodo Plachter Petra Hoffmann Angelique Renzaho Matthias Theobald Matthias J Reddehase Wolfgang Herr Niels A W Lemmermann Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice. PLoS Pathogens |
| 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 |
| url | http://europepmc.org/articles/PMC4504510?pdf=render |
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