Prolonged survival of rat islet xenografts in mice after CD45RB monotherapy.

Abstract

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