Thomas, Simone and Klobuch, Sebastian and Podlech, Juergen and Plachter, Bodo and Hoffmann, Petra and Renzaho, Angelique and Theobald, Matthias and Reddehase, Matthias J. and Herr, Wolfgang and Lemmermann, Niels A. W. (2015) Evaluating Human T-Cell Therapy of Cytomegalovirus Organ Disease in HLA-Transgenic Mice. PLOS PATHOGENS, 11 (7): e1005049. ISSN 1553-7366, 1553-7374
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | IMMUNE EVASION PROTEINS; BONE-MARROW-TRANSPLANTATION; MURINE CYTOMEGALOVIRUS; ADOPTIVE IMMUNOTHERAPY; PREEMPTIVE IMMUNOTHERAPY; ANTIGEN PRESENTATION; VIRAL REPLICATION; ANIMAL-MODELS; HIGH-AFFINITY; INFECTION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 08 Jul 2019 08:11 |
| Last Modified: | 08 Jul 2019 08:11 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5234 |
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