Regulation of human auto- and alloreactive T cells by indoleamine 2,3-dioxygenase (IDO)–producing dendritic cells: too much ado about IDO?

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Abstract
Although dendritic cells (DCs) strongly stimulate the immune response, they can also induce unresponsiveness. Recently, a human monocyte-derived DC subpopulation was described that constitutively expresses indoleamine 2,3-dioxygenase (IDO). These DCs were defined as nonadherent CD123+/CC chemokine receptor 6+ (CCR6+) cells that suppress the allogeneic T-cell response. In the present study, we generated nonadherent, mature DCs from human blood monocytes. As expected, in addition to the classic markers, these cells expressed CD123 and CCR6. Reverse transcription–polymerase chain reaction (RT-PCR), however, did not show IDO gene transcription, nor did we detect enzymatic IDO activity. Treating the cells with interferon-γ (IFN-γ) 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 preactivated 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 nonadherent CD123+/CCR6+ human DCs do not constitutively express IDO, and, even if they express the enzyme after IFN-γ treatment, they possess only limited T-cell regulatory function.