Abstract 11956: Thioredoxin-Priming Induces Allogeneic Tolerance in a Rat Model of Lung Transplantation
Allogeneic-specific tolerance is the final goal of transplant medicine. We recently reported that priming donor lungs with Thioredoxin-1(Trx) drastically protected the allograft in a rat model of allogeneic lung transplant. To assess whether allogeneic immune tolerance is induced, we performed lung transplant in an allogeneic rat model under no immunosppresion. Recipients received allogeneic grafts pre-treated with perfusion and storage in Perfadex solution with or without Trx at 4° C for 4 hr. At different time points post-surgery, recipients were euthanized. And assessed for lung histology and immunological activities. We found that allografts without Trx-priming showed grade 3.6 acute rejection, whereas Trx-primed allografts only showed grade 2.2 acute rejection five days post-transplant. One week post-transplant,allografts without Trx priming showed global necrosis,but allografts primed with Trx showed grade 2-3 acute rejection. With longer observation, allografts primed with Trx remained functional in certain areas while lung grafts in control group completely lose function with extensive fibrosis. Recipient splenic T cells showed about 30% increase of CD4+Foxp3+ regulatory T cells in Trx group compared to controls. In allo-MLR, CD4+ T cells from animals receiving Trx-primed donor lung responded poorly to the stimulation of allogeneic splenic dendritic cells (DCs) relative to those from the control animals. However, CD4+ T cells from both groups responded well and with equivalent levels to the stimulation of splenic DCs from the third party, suggesting donor alloantigen specific tolerance was induced. This non-invasive approach is highly clinically translatable and may benefit lung and/or other solid organ transplantation.
- © 2011 by American Heart Association, Inc.