Browsing by Subject "Transplantation Tolerance"

Now showing 1 - 2 of 2

Open Access
Lung Transplantation and the Era of the Sensitized Patient.
(Frontiers in immunology, 2021-01) Young, Katherine A; Ali, Hakim A; Beermann, Kristi J; Reynolds, John M; Snyder, Laurie D
Long term outcomes in lung transplant are limited by the development of chronic lung allograft dysfunction (CLAD). Within the past several decades, antibody-mediated rejection (AMR) has been recognized as a risk factor for CLAD. The presence of HLA antibodies in lung transplant candidates, "sensitized patients" may predispose patients to AMR, CLAD, and higher mortality after transplant. This review will discuss issues surrounding the sensitized patient, including mechanisms of sensitization, implications within lung transplant, and management strategies.
Open Access
Murine cytomegalovirus dissemination but not reactivation in donor-positive/recipient-negative allogeneic kidney transplantation can be effectively prevented by transplant immune tolerance.
(Kidney international, 2020-07) Dangi, Anil; Yu, Shuangjin; Lee, Frances T; Burnette, Melanie; Wang, Jiao-Jing; Kanwar, Yashpal S; Zhang, Zheng J; Abecassis, Michael; Thorp, Edward B; Luo, Xunrong
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.