Birgit Jürgens¹, Julia Raberger¹, Dietmar Fuchs² and Andreas Heitger¹

Children’s Cancer Research Institute, Division Transplantation Immunology, Zimmermannplatz 10, A-1090 Vienna, Austria. 2Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Austria.

Abstract

In recent years tryptophan metabolism and its rate limiting enzyme indoleamine 2,3-dioxygenase (IDO) have attracted increasing attention for their potential to modulate immune responses including the regulation of transplantation tolerance. The focus of this review is to discuss some features of IDO activity which particularly relate to hematopoietic stem cell transplantation (HSCT). HSCT invariably involves the establishment of some degree of a donor-derived immune system in the recipient. Thus, the outstanding feature of tolerance in HSCT is that in this type of transplantation it is not rejection, which causes the most severe problems to HSCT recipients, but the reverse, graft-versus-host (GvH) directed immune responses. We will discuss the peculiar role of IDO activity and accelerated tryptophan metabolism at the interface between immune activation and immune suppression and delineate from theoretical and experimental evidence the potential significance of IDO in mediating tolerance in HSCT. Finally, we will examine therapeutic options for exploitation of IDO activity in the generation of allo-antigen-specific tolerance, i.e. avoiding allo-reactivity while maintaining immunocompetence, in HSCT.