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CUTTING EDGE |
Departments of
*
Medicine and
Pediatrics, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912;
Lexicon Genetics, The Woodlands, TX 77381; and
The Institute of Physical and Chemical Research, Research Center for Allergy and Immunology, Suehirocho, Tsurumi-ku, Yokohama, Japan
In mice, immunoregulatory APCs express the dendritic cell (DC) marker CD11c, and one or more distinctive markers (CD8
, 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.
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D. H. Munn, M. D. Sharma, and A. L. Mellor Ligation of B7-1/B7-2 by Human CD4+ T Cells Triggers Indoleamine 2,3-Dioxygenase Activity in Dendritic Cells J. Immunol., April 1, 2004; 172(7): 4100 - 4110. [Abstract] [Full Text] [PDF]
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