Transplantation: moving to the next level

This issue of Immunological Reviews bridges two traditionally separate fields. While the average immunologist may think of “transplantation” as a single entity, it has, for largely practical reasons, been split into two separate fields, namely hematopoietic cell transplantation (HCT) and organ transplantation. In allogeneic HCT, which was originally used as a rescue therapy for the marrow toxicity of high-dose chemotherapy and/or irradiation employed to treat a hematologic malignancy, the recipient’s immune system is severely compromised and the greatest concern has been the attack of immune cells in the donor inoculum on the severely immunocompromised recipient. This attack, which caused the sometimes fatal syndrome known as graft-vs-host disease (GVHD), was so severe when HLA barriers were transgressed that until recently the practice of HCT has been largely confined to the HLA-identical or near-identical donor situation, severely limiting the availability of this curative therapy. Even in the present day, as approaches to performing HLA-mismatched HCT have permitted more widespread transplantation in this setting, the incidence of significant GVHD is in the 30–40% range in the least immunogenic combination involving HLA-identical sibling donors, despite the use of pharmacologic immunosuppression as GVHD prophylaxis(1). Thus, GVHD remains a major cause of morbidity and mortality following HCT.