Acute murine cytomegalovirus disrupts established transplantation tolerance and causes recipient allo-sensitization.

Journal Article (Journal Article)

We have previously shown that acute cytomegalovirus (CMV) infection disrupts the induction of transplantation tolerance. However, what impact acute CMV infection would have on the maintenance of established tolerance and on subsequent recipient allo-sensitization is a clinically important unanswered question. Here we used an allogeneic murine islet transplantation tolerance model to examine the impact of acute CMV infection on: (a) disruption of established transplantation tolerance during tolerance maintenance; and (b) the possibility of recipient allo-sensitization by CMV-mediated disruption of stable tolerance. We demonstrated that acute CMV infection abrogated transplantation tolerance during the maintenance stage in 50%-60% recipients. We further demonstrated that acute CMV infection-mediated tolerance disruption led to recipient allo-sensitization by reverting the tolerant state of allo-specific T cells and promoting their differentiation to allo-specific memory cells. Consequently, a second same-donor islet allograft was rejected in an accelerated fashion by these recipients. Our study therefore supports close monitoring for allo-sensitization in previously tolerant transplant recipients in whom tolerance maintenance is disrupted by an episode of acute CMV infection.

Full Text

Duke Authors

Cited Authors

  • Yu, S; Dangi, A; Burnette, M; Abecassis, MM; Thorp, EB; Luo, X

Published Date

  • February 2021

Published In

Volume / Issue

  • 21 / 2

Start / End Page

  • 515 - 524

PubMed ID

  • 32659030

Pubmed Central ID

  • PMC7855505

Electronic International Standard Serial Number (EISSN)

  • 1600-6143

Digital Object Identifier (DOI)

  • 10.1111/ajt.16197

Language

  • eng

Conference Location

  • United States