Blockade of the passive cell death pathway does not prevent tolerance induction to islet grafts.
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.
Lehnert
Anne M
AM
Centre for Transplant and Renal Research, Westmead Millennium Institute, University of Sydney at Westmead Hospital, New South Wales, Australia.
Murray-Segal
Lisa
L
Cowan
Peter J
PJ
d'Apice
Anthony J
AJ
O'Connell
Philip J
PJ
D000069594:Abatacept; D000818:Animals; D030801:Animals, Genetically Modified; D016923:Cell Death / Q000502:physiology*; D006085:Graft Survival; D006801:Humans; D007108:Immune Tolerance; D018796:Immunoconjugates / Q000235:genetics; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051381:Rats
D018796:Immunoconjugates; D019253:Proto-Oncogene Proteins c-bcl-2; D000069594:Abatacept