Therapeutic approaches for transplantation.

Developments in marrow and organ transplantation are mutually interactive. There have been several recent advances in stem cell transplantation: to ensure engraftment using larger doses of stem cells; to substantially reduce the incidence of graft-versus-host disease and marrow rejection using monoclonal antibodies; and to reduce toxicity of the preparative regimen through use of so-called nonmyeloablative regimens (mini-transplants). These advances may pave the way for generation of mixed hemopoietic chimerism as an aid to achieving tolerance to organ transplants. The use of short courses of T-cell-depleting antibodies, such as CD3 immunotoxin in primates and CAMPATH-1H in humans, has demonstrated that long-term graft survival may be possible without substantive long-term immunosuppressive treatment of the recipient. The demonstration in rodents that nondepleting antibodies to T cells can give rise to powerful regulatory mechanisms that maintain tolerance to grafts has initiated a major research effort in understanding how these regulatory T cells work, with the prospect of new therapeutic modalities to mimic or enhance their function.