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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2480-2486.
Prepublished online as a Blood First Edition Paper on November 30, 2004; DOI 10.1182/blood-2004-06-2103.
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Submitted June 14, 2004
Accepted November 17, 2004
Regulation of human auto- and alloreactive T cells by indoleamine 2,3-dioxygenase (IDO)-producing dendritic cells: too much ado about IDO?
Peter Terness*, Jing-Jing Chuang, Thomas Bauer, Lucian Jiga, and Gerhard Opelz
Institute of Immunology, Department of Transplantation Immunology, University of Heidelberg, Heidelberg, Germany
* Corresponding author; email: peter.terness{at}med.uni-heidelberg.de.
Although dendritic cells (DCs) strongly stimulate the immune response, they can also induce unresponsiveness. Recently, a human monocyte-derived DC subpopulation was described which constitutively expresses IDO. These DCs were defined as non-adherent, CD123+, CCR6+ cells, which suppress the allogeneic T-cell response. In the present study we generated non-adherent, mature DCs from human blood monocytes. As expected, in addition to the classical markers, these cells expressed CD123 and CCR6. RT-PCR, however, did not show IDO-gene transcription, nor did we detect enzymatic IDO-activity. Treating the cells with IFN- resulted in significant IDO production. Subsequently, we studied the regulatory properties of IDO-producing DCs on autologous and allogeneic T-cell responses. Neither OKT3-stimulated T cells of healthy donors nor myelin basic protein (=MBP)-specific T cells of patients with multiple sclerosis (=MS) were suppressed by autologous IDO-DCs. However, whereas IDOneg DCs supported further stimulation of pre-activated MBP-specific T cells of an MS patient, IDOpos DCs had lost this capacity. The allogeneic T-cell response was only marginally suppressed by IDO-DCs. Our findings show that non-adherent, CD123+, CCR6+ human DCs do not constitutively express IDO and, even if they express the enzyme after IFN- treatment, posses only limited T-cell regulatory function.

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