Document Detail

Blockade of the passive cell death pathway does not prevent tolerance induction to islet grafts.
MedLine Citation:
PMID:  17353789     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: T-cell apoptosis is an important regulatory mechanism in transplant tolerance. The aim of this study was to identify specific apoptotic molecules important for tolerance induction.
METHODS: Mice expressing the human Bcl-2 molecule in T cells or Bim -/- mice were used as islet allograft or rat islet xenograft recipients and treated with CTLA4-Fc and MR1 costimulation blockade.
RESULTS: hBcl-2 transgenic mice and Bim -/- accepted islet allografts and rat islet xenografts for more than 100 days, similar to wildtype controls. Changes in the dose of the CTLA4-Fc and MR1 did not lead to differences in graft survival and there were no differences in the percentage of CD4+ T cells expressing Fas, CD25, or undergoing apoptosis.
CONCLUSIONS: Inhibition of the passive cell death pathway in T cells did not block tolerance induction, suggesting that the mechanism by which apoptosis regulates the alloimmune response is more complex than first thought.
Anne M Lehnert; Lisa Murray-Segal; Peter J Cowan; Anthony J d'Apice; Philip J O'Connell
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Transplantation     Volume:  83     ISSN:  0041-1337     ISO Abbreviation:  Transplantation     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-03-13     Completed Date:  2007-04-20     Revised Date:  2013-05-24    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  653-5     Citation Subset:  IM    
Centre for Transplant and Renal Research, Westmead Millennium Institute, University of Sydney at Westmead Hospital, New South Wales, Australia.
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MeSH Terms
Animals, Genetically Modified
Cell Death / physiology*
Graft Survival
Immune Tolerance*
Immunoconjugates / genetics
Islets of Langerhans Transplantation / immunology*
Mice, Transgenic
Proto-Oncogene Proteins c-bcl-2 / genetics
Reg. No./Substance:
0/Immunoconjugates; 0/Proto-Oncogene Proteins c-bcl-2; 7D0YB67S97/abatacept

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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