Paradoxical Aspects of Rapamycin Immunobiology in Transplantation

• Type of Material: Article
• Authors: Ivana R. Ferrer, Emory University; Koichi Araki, Emory University; Mandy L Ford, Emory University
• Language: English
• Date: 2011-04
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: ©2011 The Authors Journal compilation ©2011 The American Society of Transplantation and the American Society of Transplant Surgeons
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1111/j.1600-6143.2011.03473.x/abstract
• Title of Journal or Parent Work: American Journal of Transplantation
• ISSN: 1600-6135
• Volume: 11
• Issue: 4
• Start Page: 654
• End Page: 659
• Grant/Funding Information: The authors were supported in part by NIAID awards AI073707 and AI81789 (to M.L.F)
• Keywords: fatty acid metabolism; survival; T cell differentiation; pathogen; dendritic cell maturation; immunosuppression
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Microbiology; Health Sciences, Immunology

Abstract

Rapamycin has long been considered an immunosuppressive agent due to its anti-proliferative effects on immune cells, and is currently used as a component of anti-rejection regimens in transplantation. Despite the large number of mechanistic and clinical studies investigating the impact of rapamycin on cell-mediated immunity, several paradoxes concerning rapamycin immunobiology remain. In particular, emerging evidence suggests that under certain circumstances rapamycin can exert immunostimulatory effects, boosting T cell responses in the face of pathogen infections and vaccines. Here, we review recent findings concerning the contradictory outcomes of rapamycin induced mTOR inhibition on CD4+ and CD8+ T cell responses in transplantation and protective immunity. These studies suggest that the conditions under which T cells are stimulated can profoundly modify the impact of rapamycin on antigen-specific T cell responses. Thus, further investigation into the cellular and molecular pathways underlying the dichotomous effects of rapamycin in transplantation is required to harness the full potential of this immunomodulatory agent to promote graft survival and maximize protective immunity.