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

• Type of Material: Article
• Authors: Steven C. Kim, Emory University; Jun Wang, Emory University; Ying Dong, Emory University; David V. Mathews, Emory University; Joshua A. Albrecht, Emory University; Cynthia P. Breeden, Emory University; Alton Farris III, Emory University; Aron E. Lukacher, Penn State College of Medicine; Mandy Ford, Emory University; Kenneth Newell, Emory University; Andrew Adams, Emory University
• Language: English
• Date: 2017-06
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Final Published Version
• Copyright Statement: Copyright © 2017 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1097/TXD.0000000000000677
• Title of Journal or Parent Work: Transplantation Direct
• ISSN: 2373-8731
• Volume: 3
• Issue: 6
• Start Page: e161
• End Page: e161
• Grant/Funding Information: This work was supported by NIH grants R01AI078426 (KAN), R01CA071971(AEL), and R01 AI102543 (AEL).
• Research Categories: Biology, Virology; Health Sciences, Immunology

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.