Prolonged survival of rat islet xenografts in mice after CD45RB monotherapy

BACKGROUND: Pancreatic islet transplantation can correct the disordered glucose metabolism of type 1 diabetes, but the number of successful transplants has been low because of the need for long-term immunosuppression and the limited availability of human islets. New approaches, such as the use of tolerance-inducing treatment modalities and the use of islets of nonhuman sources, can possibly improve the success of islet transplantation. In the present study, the authors investigated the effect of anti-CD45RB treatment on the survival of islet xenografts.

METHODS: Chemically induced diabetic mice underwent xenografting with rat islets and were treated with CD45RB antibodies on days -1, 0, and 5. Immunohistology and real-time polymerase chain reaction were used to study the effect of the treatment in the xenografts. The effect of anti-CD45RB treatment in peripheral blood of normal mice was measured with flow cytometry.

RESULTS: In the treated mice, survival of the grafts was prolonged substantially. In the treated mice with functioning grafts, no lymphocytes were found infiltrating the transplanted islets on day 6; whereas in the untreated animals with functioning grafts, signs of rejection were evident. In the grafts of the treated animals, significantly less mRNA for interleukin (IL)-2, interferon-gamma, and IL-4 was found compared with the untreated mice. After CD45RB treatment, there was depletion or decrease of CD45RBbright cells from the peripheral blood.

CONCLUSIONS: Our results show that a short course of anti-CD45RB monotherapy prolongs the survival of rat islet xenografts in C57BL/6 mice.