Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall C & D
*Purpose: In liver transplantation (LT), acute rejection (AR) remains a common complication that significantly shortens recipient survival although various immunosuppressors have been used in clinical practice. In recent years, manipulating immune tolerance has been regarded as one of the promising solutions. Autophagy, an evolutionarily conserved protein degrading system, has been reported to be involved in the immune rejection and may become a target to establish immune tolerance. However, its role in AR after LT has not been elucidated.
*Methods: Human liver tissues from patients with AR and control individuals were obtained to evaluate autophagy specific protein LC3 expression. Acute rejection model was established in rats to analyze the exact role of autophagy in AR. In addition, the underlying mechanism autophagy participated in AR were further explored by ex vivo study.
*Results: The autophagy of CD8+ T cell was strongly enhanced in patients with AR and autophagy level was positively correlated with the severity of rejection. Similar findings were observed in the acute rejection rat model. Furthermore, administration of autophagy inhibitor 3methyladenine(3MA) significantly prolonged graft survival through inhibiting autophagy of CD8+ T cell, which resulted in decreased viability and function of CD8+ T cell. In addition, inhibition of autophagy of activated CD8+ T cells largely reduced the stabilization of intact mitochondria and subsequently increased the production of mitochondrial superoxide (MitoSOX) in vitro.
*Conclusions: We firstly showed inhibiting autophagy significantly prolongs liver allograft survival by accelerating apoptosis of CD8+ T cells , which will provide a novel strategy for immune tolerance induction.
To cite this abstract in AMA style:Chen X, Yang Q, Li X, Deng Y, Chen G, Wang G. Inhibition of Autophagy Prolongs Recipients Survival through Accelerating CD8+ T Cell Apoptosis in a Rat Liver Transplantation Model [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/inhibition-of-autophagy-prolongs-recipients-survival-through-accelerating-cd8-t-cell-apoptosis-in-a-rat-liver-transplantation-model/. Accessed July 12, 2020.
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