CTLA4Ig ATTENUATES ACCELERATED REJECTION (PRESENSITIZATION) IN THE MOUSE ISLET ALLOGRAFT MODEL1

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Abstract
Sensitization to donor antigens is a problem of growing magnitude in clinical transplantation. At a molecular level, this is due to the interaction between antigen bearing antigen-presenting cells and recipient T cells and involves both antigen presentation and co-stimulation. Allogeneic islet transplantation was performed using DBA/2J donors and B6AF1 recipients. Four weeks before transplantation, recipient animals were given donor-specific transfusion (DST) alone, DST + CTLA4Ig, DST + control IgG, or no treatment. Graft loss was defined as a blood glucose >300 mg/100 ml. Administration of DST + control IgG 4 weeks before transplantation resulted in accelerated rejection due to presensitization (median survival time of 8 days, compared with 14.5 days for the notreatment group). Animals treated with CTLA4Ig in combination with DST had a median survival time of 12 days, compared with 8 days for DST + IgG. CTLA4Ig attenuates the tempo of accelerated rejection in this islet allograft model of presensitization, but does not prolong allograft survival as compared with no treatment.