Long-term graft function of adult rat islets after transplantation in immunocompetent diabetic mice treated with donor specific splenocytes and anti-CD154 monoclonal antibody

Aim: Combined treatment with a single donor specific transfusion (DST) and a brief course of anti-mouse CD154 monoclonal antibody (mAb) to induce co-stimulation blockade leeds to long-term islet allograft survival in mice. We hypothesized that this protocol could also induce long-term graft survival of adult rat islets in immunocompentent diabetic mice.

Material and Methods: Rat islets were isolated from CD-rats and cultured for 48h at 37°C. In each case 600 rat islets were transplanted to the renal subcapsular space. Recipients were chemically diabetic Balb/c mice that were otherwise untreated, treated with DST alone, or treated with DST plus anti-CD154 mAb. Blood glucose concentrations and body weight were measured twice weekly, and xenografts were examined histologically.

Results: While in untreated diabetic Balb/c mice rat islets lost function approximately 7 days after transplantation, in mice treated with DST and a brief course of anti-CD154 mAb the transplantation of rat islets resulted in normoglyceamia for more than 70 days. Surviving grafts were essentially free of inflammatory infiltrates 50 days after transplantation.

Conclusions: We have developed a strategy with a single DST and a brief course of anti-mouse CD154 mAb that enables survival and function of xenografts without maintenance immunosuppression.