CTLA4IG ATTENUATES ACCELERATED REJECTION (PRESENSITIZATION) IN THE MOUSE ISLET ALLOGRAFT MODEL

Background. Sensitization to donor antigens is a problem of growing ma gnitude in clinical transplantation. At a molecular level, this is due to the interaction between antigen bearing antigen-presenting cells a nd recipient T cells and involves both antigen presentation and co-sti mulation. Methods. Allogeneic islet transplantation was performed usin g DBA/2J donors and B6AF1 recipients. Four weeks before transplantatio n, recipient animals were given donor-specific transfusion (DST) alone , DST + CTLA4Ig, DST + control IgG, or no treatment. Graft loss was de fined as a blood glucose >300 mg/100 mi. Results. Administration of DS T + control IgG 4 weeks before transplantation resulted in accelerated rejection due to presensitization (median survival time of 8 days, co mpared with 14.5 days for the no-treatment group). Animals treated wit h CTLA4Ig in combination with DST had a median survival time of 12 day s, compared with 8 days for DST + IgG. Conclusions. CTLA4Ig attenuates the tempo of accelerated rejection in this islet allograft model of p resensitization, but does not prolong allograft survival as compared w ith no treatment.