Indoleamine 2,3-Dioxygenase in Hematopoietic Stem Cell Transplantation

U.      Hainz; B.      Jurgens; T.      Wekerle; M.   G.   Seidel; Andreas      Heitger

doi:10.2174/138920007780362554

Abstract

Hematopoietic stem cell transplantation (HSCT) is complicated by unwelcome side-effects that arise on the basis of an altered immune system. Infectious complications and alloreactive T-cell responses trigger a process of ongoing immune activation and inflammation. Negative-feedback mechanisms to counteract inflammation involve the induction of the immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO), which mediates anti-inflammatory activities and T-cell inhibition via tryptophan catabolism. However, persistent immune activation and generalized release of pro-inflammatory cytokines deviate immune regulation towards chronic suppression incapable to abrogate the inflammatory response. This review focuses on the unique role of tryptophan catabolism in modulating inflammatory processes and T-cell responses after HSCT.

Keywords: Indoleamine 2,3-dioxygenase, HSCT, T-cell, transplantation, tolerance, inflammation, CTLA4, GVHD