Transplantation Without Immunosuppression

Exciting new findings have been reported in the past few years that indicate that islets can he transplanted successfully across major histocompatibility harriers without the continuous use of imrnunosuppressive agents by techniques designed to eliminate passenger leukocytes, in vitro culture of donor islets either at a low temperature (24°C) with a single injection of anti-lymphocyte serum or culture of megaislets in the presence of 95% O₂ before transplantation permitted the successful transplantation of islet allograft and xenografts (rat to mouse). Definitive evidence in support of the passenger leukocyte concept has been obtained recently. Mouse islet cells have been shown to express the class I antigens of the H-2 complex, but do not express la antigens. Treatment of fresh mouse islets with specific anti-la sera and complement completely prevented rejection of islets transplanted across a major histocompatibility barrier. These findings indicate that la-positive cells (possibly dendritic cells) are primarily responsible for the initiation of immune rejection of the transplants. This is of particular importance with respect to the eventual transplantation of islets into human diabetics since it may be feasible to utilize antisera to HLA-DR antigens for pretreatment of islets before transplantation. In addition, these new developments may also be applicable to the transplantation of other organs such as the parathyroid, heart, kidney, liver, and skin.