Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25- into CD25+ T regulatory cells.

摘要: Indoleamine 2,3-dioxygenase (IDO) is a novel immunosuppressive agent expressed in some subsets of normal and neoplastic cells, including acute myeloid leukemia (AML) cells. Here, we show that IDO expression correlates with increased circulating CD4CD25FOXP3 T cells patients AML at diagnosis. In vitro, increase the number CD4 CD25 expressing surface CTLA-4 FOXP3 mRNA, this effect completely abrogated by inhibitor, 1-methyl tryptophan (1-MT). Purified CD4CD25 obtained from coculture act as regulatory (Treg) because they do not proliferate, produce interleukin (IL)‐2, inhibit naive T-cell proliferation. Coculture IDOAML results conversion into which 1-MT. Moreover, mice, intrasplenic injection leukemia/ lymphoma A20 induces expansion bona fide Treg cells; counteracted 1-MT treatment. These data indicate thatAML induce tolerance directly converting through an IDO-dependent mechanism. (Blood. 2007;109:2871-2877)