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Alloimmunity But Not Viral Immunity Promotes Allograft Loss in a Mouse Model of Polyomavirus-Associated Allograft Injury
BACKGROUND: The interplay between viral infection and alloimmunity is known to influence the fate of transplanted organs. Clarifying how local virus-associated inflammation/injury and antiviral immunity can alter host alloimmune responses in transplantation remains a critical question. METHODS: We u...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464780/ https://www.ncbi.nlm.nih.gov/pubmed/28620645 http://dx.doi.org/10.1097/TXD.0000000000000677 |
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author | Kim, Steven C. Wang, Jun Dong, Ying Mathews, David V. Albrecht, Joshua A. Breeden, Cynthia P. Farris, Alton B. Lukacher, Aron E. Ford, Mandy L. Newell, Kenneth A. Adams, Andrew B. |
author_facet | Kim, Steven C. Wang, Jun Dong, Ying Mathews, David V. Albrecht, Joshua A. Breeden, Cynthia P. Farris, Alton B. Lukacher, Aron E. Ford, Mandy L. Newell, Kenneth A. Adams, Andrew B. |
author_sort | Kim, Steven C. |
collection | PubMed |
description | BACKGROUND: The interplay between viral infection and alloimmunity is known to influence the fate of transplanted organs. Clarifying how local virus-associated inflammation/injury and antiviral immunity can alter host alloimmune responses in transplantation remains a critical question. METHODS: We used a mouse model of polyomavirus (PyV) infection and kidney transplantation to investigate the roles of direct viral pathology, the antiviral immune response, and alloimmunity in the pathogenesis of PyV-associated allograft injury. We have previously shown that an effective primary T cell response is required in PyV-associated graft injury. RESULTS: Here we show that the transfer of primed antidonor, but not antiviral, T cells results in PyV-associated allograft injury. In further studies, we use a surrogate minor antigen model (ovalbumin) and show that only antidonor specific T cells and not antiviral specific T cells are sufficient to mediate injury. Lastly, we demonstrate that local but not systemic virus-mediated inflammation and injury within the graft itself are required. CONCLUSIONS: These data suggest that in this mouse model, the predominant mechanism of allograft injury in PyV-associated injury is due to an augmented alloimmune T cell response driven by virus-induced inflammation/injury within the graft. These studies highlight the important interplay between viral infection and alloimmunity in a model system. |
format | Online Article Text |
id | pubmed-5464780 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-54647802017-06-15 Alloimmunity But Not Viral Immunity Promotes Allograft Loss in a Mouse Model of Polyomavirus-Associated Allograft Injury Kim, Steven C. Wang, Jun Dong, Ying Mathews, David V. Albrecht, Joshua A. Breeden, Cynthia P. Farris, Alton B. Lukacher, Aron E. Ford, Mandy L. Newell, Kenneth A. Adams, Andrew B. Transplant Direct Basic Science BACKGROUND: The interplay between viral infection and alloimmunity is known to influence the fate of transplanted organs. Clarifying how local virus-associated inflammation/injury and antiviral immunity can alter host alloimmune responses in transplantation remains a critical question. METHODS: We used a mouse model of polyomavirus (PyV) infection and kidney transplantation to investigate the roles of direct viral pathology, the antiviral immune response, and alloimmunity in the pathogenesis of PyV-associated allograft injury. We have previously shown that an effective primary T cell response is required in PyV-associated graft injury. RESULTS: Here we show that the transfer of primed antidonor, but not antiviral, T cells results in PyV-associated allograft injury. In further studies, we use a surrogate minor antigen model (ovalbumin) and show that only antidonor specific T cells and not antiviral specific T cells are sufficient to mediate injury. Lastly, we demonstrate that local but not systemic virus-mediated inflammation and injury within the graft itself are required. CONCLUSIONS: These data suggest that in this mouse model, the predominant mechanism of allograft injury in PyV-associated injury is due to an augmented alloimmune T cell response driven by virus-induced inflammation/injury within the graft. These studies highlight the important interplay between viral infection and alloimmunity in a model system. Lippincott Williams & Wilkins 2017-05-12 /pmc/articles/PMC5464780/ /pubmed/28620645 http://dx.doi.org/10.1097/TXD.0000000000000677 Text en Copyright © 2017 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | Basic Science Kim, Steven C. Wang, Jun Dong, Ying Mathews, David V. Albrecht, Joshua A. Breeden, Cynthia P. Farris, Alton B. Lukacher, Aron E. Ford, Mandy L. Newell, Kenneth A. Adams, Andrew B. Alloimmunity But Not Viral Immunity Promotes Allograft Loss in a Mouse Model of Polyomavirus-Associated Allograft Injury |
title | Alloimmunity But Not Viral Immunity Promotes Allograft Loss in a Mouse Model of Polyomavirus-Associated Allograft Injury |
title_full | Alloimmunity But Not Viral Immunity Promotes Allograft Loss in a Mouse Model of Polyomavirus-Associated Allograft Injury |
title_fullStr | Alloimmunity But Not Viral Immunity Promotes Allograft Loss in a Mouse Model of Polyomavirus-Associated Allograft Injury |
title_full_unstemmed | Alloimmunity But Not Viral Immunity Promotes Allograft Loss in a Mouse Model of Polyomavirus-Associated Allograft Injury |
title_short | Alloimmunity But Not Viral Immunity Promotes Allograft Loss in a Mouse Model of Polyomavirus-Associated Allograft Injury |
title_sort | alloimmunity but not viral immunity promotes allograft loss in a mouse model of polyomavirus-associated allograft injury |
topic | Basic Science |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464780/ https://www.ncbi.nlm.nih.gov/pubmed/28620645 http://dx.doi.org/10.1097/TXD.0000000000000677 |
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