Immune reconstitution: The major barrier to successful stem cell transplantation

Abstract

m p g p r a i s i p c s f b u a T f m t l m s t p c The numerous advances in our understanding of ransplantation biology combined with enhancements n supportive care have substantially improved the ealth of our patients. Transplant-related morbidity as progressively declined over the last 30 years, and his can be at least in part measured by our ability to rovide stem cell transplantation to an aging populaion and by our fledgling ability to cross histocompatbility barriers. However, a persistently frustrating imitation in transplantation medicine is delayed, indequate, or incomplete reconstitution of the immune ystem. Patients die of opportunistic infections despite ell-controlled graft-versus-host disease (GVHD) nd eradication of the underlying disease. Although VHD control, improvements in antibiotic spectra, nd circumspection in the use of immunosuppressants ave helped, too many patients still die of infections ecause of insufficient immunologic recovery. Immunologic recovery and GVHD are intrinsially linked. It is helpful to think of acute GVHD as an nflammatory disorder in which T cells from the door behave appropriately in the context in which they nd themselves. In other words, the donor’s T cells ecognize minor histocompatibility antigens in the etting of upregulated adhesion molecules, inflammaory cytokines, and damaged epithelia. Thus, the T ell’s view of the world is that the host is seriously nfected, and its job is to respond to this infection by nitiating and sustaining an effective immune reponse. Of course, the problem is that the effective mmune response is directed against minor histocomatibility differences rather than microbial proteins. his response is maladaptive from the perspective of a ransplant clinician. We want the T cells to identify iral, bacterial, and fungal products in the context of ajor histocompatibility complex but not minor hisocompatibility antigens per se. The T cell may not be t