Alloimmunity but Not Viral Immunity Promotes Allograft Loss in a Mouse Model of Polyomavirus-Associated Allograft Injury

Steven C. Kim, Jun Wang, Ying Dong, David V. Mathews, Joshua A. Albrecht, Cynthia P. Breeden, Alton B. Farris, Aron E. Lukacher, Mandy L. Ford, Kenneth A. Newell, Andrew B. Adams

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)E161
JournalTransplantation Direct
Volume3
Issue number6
DOIs
StatePublished - Jun 1 2017
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by NIH grants R01AI078426 (KAN), R01CA071971(AEL), and R01 AI102543 (AEL).

Publisher Copyright:
Copyright © 2017 The Author(s).

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