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

We have previously shown that acute cytomegalovirus (CMV) infection disrupts theinductionof transplantation tolerance. However, what impact acute CMV infection would have on themaintenanceof 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.

Automated summary

Acute CMV infection disrupts established transplantation tolerance in 50%-60% of recipients during the maintenance stage and leads to recipient allo-sensitization. This disruption reverts allo-specific T cells to a non-tolerant state and promotes their differentiation into allo-specific memory cells, resulting in accelerated rejection of a second same-donor islet allograft. Close monitoring for allo-sensitization is recommended in previously tolerant transplant recipients with disrupted tolerance maintenance due to acute CMV infection.