Document Detail


Paradoxical aspects of rapamycin immunobiology in transplantation.
MedLine Citation:
PMID:  21446969     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Rapamycin has long been considered an immunosuppressive agent due to its antiproliferative effects on immune cells, and is currently used as a component of antirejection 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.
Authors:
I R Ferrer; K Araki; M L Ford
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons     Volume:  11     ISSN:  1600-6143     ISO Abbreviation:  Am. J. Transplant.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-30     Completed Date:  2011-08-16     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  100968638     Medline TA:  Am J Transplant     Country:  United States    
Other Details:
Languages:  eng     Pagination:  654-9     Citation Subset:  IM    
Copyright Information:
©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.
Affiliation:
Emory Transplant Center and Department of Surgery Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Graft Survival / drug effects*,  physiology*
Humans
Immunity, Cellular / drug effects*
Immunosuppressive Agents / pharmacology*
Organ Transplantation*
Sirolimus / pharmacology*
T-Lymphocytes / drug effects*
Grant Support
ID/Acronym/Agency:
AI073707/AI/NIAID NIH HHS; AI81789/AI/NIAID NIH HHS; R01 AI073707/AI/NIAID NIH HHS; R56 AI081789/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Immunosuppressive Agents; 53123-88-9/Sirolimus
Comments/Corrections

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