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 expres..