Blockade of the passive cell death pathway does not prevent tolerance induction to islet grafts.

ABSTRACT

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.