کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3392175 | 1592680 | 2012 | 5 صفحه PDF | دانلود رایگان |
Cardiac allograft vasculopathy (CAV) is the leading cause of late morbidity and mortality in heart-transplant patients. Increasing evidences support the important role of chemokines and their receptors in transplant immunology. Chemokine–chemokine receptor interaction and subsequent recruitment of T-lymphocytes to the graft are early events in the development of chronic rejection of transplanted hearts. In this study, we first inhibited CC-motif chemokine receptor 5 (CCR5) expression by using lentiviral-mediated gene transfer of an anti-CCR5 siRNA, which introduced through CD34+ hematopoietic stem/progenitor cell transplantation. Stably marked lymphocytes expressing siRNA and consistent downregulation of CCR5 expression were detected. Our results showed that survival was significantly prolonged in CCR5 knock-down mice and donor hearts from siRNA-treated mice developed markedly less CAV. Infiltration of CD4+ and CD8+ T-lymphocytes into transplanted hearts was also markedly decreased. These findings suggest that CCR5 plays an important role in CAV development and inhibition of this chemokine could improve long-term survival after cardiac transplantation.
► Inhibition of CCR5 could improve long-term survival after cardiac transplantation.
► CTL activity of CD8+ T-cells was attenuated in CCR5−/− recipients.
► CCR5 plays a significant role in CAV development.
Journal: Transplant Immunology - Volume 26, Issues 2–3, March 2012, Pages 128–132