title: Cutting edge: induced indoleamine 2,3 dioxygenase expression in dendritic cell subsets suppresses T cell clonal expansion.
abstract: In mice, immunoregulatory APCs express the dendritic cell (DC) marker CD11c, and one or more distinctive markers (CD8alpha, B220, DX5). In this study, we show that expression of the tryptophan-degrading enzyme indoleamine 2,3 dioxygenase (IDO) is selectively induced in specific splenic DC subsets when mice were exposed to the synthetic immunomodulatory reagent CTLA4-Ig. CTLA4-Ig did not induce IDO expression in macrophages or lymphoid cells. Induction of IDO completely blocked clonal expansion of T cells from TCR transgenic mice following adoptive transfer, whereas CTLA4-Ig treatment did not block T cell clonal expansion in IDO-deficient recipients. Thus, IDO expression is an inducible feature of specific subsets of DCs, and provides a potential mechanistic explanation for their T cell regulatory properties.
authors.affiliation: Department of Medicine, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA. amellor@mail.mcg.edu
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Mellor
authors.forename: Babak
authors.initials: B
authors.lastname: Baban
authors.forename: Phillip
authors.initials: P
authors.lastname: Chandler
authors.forename: Brendan
authors.initials: B
authors.lastname: Marshall
authors.forename: Kanchan
authors.initials: K
authors.lastname: Jhaver
authors.forename: Anna
authors.initials: A
authors.lastname: Hansen
authors.forename: Pandelakis A
authors.initials: PA
authors.lastname: Koni
authors.forename: Makio
authors.initials: M
authors.lastname: Iwashima
authors.forename: David H
authors.initials: DH
authors.lastname: Munn
mesh_terms: D000069594:Abatacept; D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000637:transplantation; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002999:Clone Cells; D003713:Dendritic Cells / Q000201:enzymology* / Q000276:immunology*; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D004790:Enzyme Induction / Q000276:immunology; D005260:Female; D006131:Growth Inhibitors / Q000008:administration & dosage; D006183:H-2 Antigens / Q000235:genetics; D018796:Immunoconjugates / Q000008:administration & dosage; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007274:Injections, Intraperitoneal; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D014366:Tryptophan Oxygenase / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D006131:Growth Inhibitors; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D018796:Immunoconjugates; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007519:Isoantigens; D000069594:Abatacept; D014366:Tryptophan Oxygenase