The role of tryptophan catabolism in acquisition and effector function of memory T cells

Indoleamine 2,3-dioxygenase (IDO) catalyzes tryptophan and suppresses adaptive immunity by inhibiting T-cell proliferation and promoting their apoptosis. This article reviews the impact of IDO on cellular immunity as well as alloimmunity and particularly discusses the role of tryptophan catabolism in the generation and function of allospecific memory T cells, as the latter pose a long-term threat to allograft survival.

IDO catalyzes tryptophan and suppresses T-cell proliferation while tryptophan metabolites induce T-cell apoptosis. IDO, therefore, suppresses adaptive immunity. Recent studies have shown that IDO overexpression suppresses allograft rejection and autoimmune diseases. Particularly, our new study has shown that IDO is capable of inhibiting the generation and function of allospecific central memory CD8+ T cells, however it does not impair effector memory CD8+ T-cell function.

IDO has several immunosuppressive properties that make it a potential candidate for use in transplantation. An effective method to deliver IDO in vivo, however, is lacking. Moreover, IDO alone is insufficient for inducing long-term allograft survival, as high expression of IDO in the graft fails to prevent acute rejection. Further studies are warranted to search for drugs that increase IDO expression in vivo or to explore strategies of prolonging the half life of IDO.