Cutting edge: induced indoleamine 2,3 dioxygenase expression in dendritic cell subsets suppresses T cell clonal expansion.
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.
Mellor
Andrew L
AL
Department of Medicine, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912, USA. amellor@mail.mcg.edu
Baban
Babak
B
Chandler
Phillip
P
Marshall
Brendan
B
Jhaver
Kanchan
K
Hansen
Anna
A
Koni
Pandelakis A
PA
Iwashima
Makio
M
Munn
David H
DH
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
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