Murine cytomegalovirus dissemination but not reactivation in donor-positive/recipient-negative allogeneic kidney transplantation can be effectively prevented by transplant immune tolerance

Anil Dangi, Shuangjin Yu, Frances T. Lee, Melanie Burnette, Jiao Jing Wang, Yashpal S. Kanwar, Zheng J. Zhang, Michael Abecassis, Edward B. Thorp, Xunrong Luo*

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Cytomegalovirus (CMV) reactivation from latently infected donor organs post-transplantation and its dissemination cause significant comorbidities in transplant recipients. Transplant-induced inflammation combined with chronic immunosuppression has been thought to provoke CMV reactivation and dissemination, although sequential events in this process have not been studied. Here, we investigated this process in a high-risk donor CMV-positive to recipient CMV-negative allogeneic murine kidney transplantation model. Recipients were either treated with indefinite immunosuppression or tolerized in a donor-specific manner. Untreated recipients served as controls. Kidney allografts from both immunosuppressed and tolerized recipients showed minimal alloimmunity-mediated graft inflammation and normal function for up to day 60 post-transplantation. However, despite the absence of such inflammation in the immunosuppressed and tolerized groups, CMV reactivation in the donor positive kidney allograft was readily observed. Interestingly, subsequent CMV replication and dissemination to distant organs only occurred in immunosuppressed recipients in which CMV-specific CD8 T cells were functionally impaired; whereas in tolerized recipients, host anti-viral immunity was well-preserved and CMV dissemination was effectively prevented. Thus, our studies uncoupled CMV reactivation from its dissemination, and underscore the potential role of robust transplantation tolerance in preventing CMV diseases following allogeneic kidney transplantation.

Original languageEnglish (US)
Pages (from-to)147-158
Number of pages12
JournalKidney international
Volume98
Issue number1
DOIs
StatePublished - Jul 2020

Keywords

  • apoptotic cell therapy
  • cytomegalovirus reactivation
  • immunosuppression
  • kidney transplant
  • transplant immune tolerance

ASJC Scopus subject areas

  • Nephrology

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