Indoleamine 2,3-dioxygenase (IDO) is an IFN-inducible enzyme that suppresses adaptive T-cell immunity by catabolizing the essential amino acid tryptophan from the cellular microenvironment. It is believed that T lymphocytes deprivation of tryptophan and generation of biologically active metabolites along the tryptophan degradation pathway cause T-cell apoptosis and preclude a T-cell response.16 IFN-α itself is supposed to be a weak inducer of IDO in antigen-presenting cells (APCs) but has an indirect effect on these cells through a yet to be defined 15-kDa protein.
This protein is a product of IFN-α-stimulated APCs and lymphocytes and stimulates both IDO and IFN-γ production. IFN-γ, in turn, is one of the most potent IDO inducers in cells of the immune system such as APCs as well as in local bystander cells such as in epithelial cells, lung cells, fibroblasts, and others. IDO expression increases when inflammation is induced by wounding, infection, or tumor growth. In infection, IDO activity was first described as a mechanism for stopping the growth of microorganisms that otherwise depend on tryptophan. Another study pointed to a role for IDO in tumor escape: expression of IDO by immunogenic tumor cells in mice prevented rejection in preimmunized recipients. Furthermore, allergic asthma bronchiale in mice could be abrogated when IDO was induced in lung epithelial cells.
