Mixed allogeneic chimerism and tolerance to composite tissue allografts

The development of effective immunosuppressive drugs has made solid organ a llotransplantation the preferred approach for treatment of end-organ failur e. The benefits of these immunosuppressants outweigh their risks in prevent ing rejection of lifesaving solid-organ allografts, On the contrary, compos ite tissue allotransplants are non-lifesaving and whether the risks of immu nosuppressants justify their benefits is a subject of debate. Hence, compos ite tissue allografts (CTA) have not enjoyed widespread clinical applicatio n for reconstruction of large tissue defects. Therefore, a method of preven ting rejection that would eliminate the need for toxic immunosuppressants i s of particular importance in CTA. Bone marrow transplantation (BMT) to est ablish mixed chimerism induces tolerance to a variety of allografts in anim al models. This article reviews mixed chimerism-based tolerance protocols. Their limitations and their relevance to CTA are discussed, highlighting so me unique characteristics thigh antigenicity and the presence of active bon e marrow) that make CTAs different from solid organ allografts. (C) 2000 Wi ley-Liss, Inc.