Are indoleamine-2,3-dioxygenase producing human dendritic cells a tool for suppression of allogeneic T-cell responses?

Abstract:

BACKGROUND:Suppressive dendritic cells (DCs) are a promising tool for tolerance induction in transplantation. A human DCs subpopulation, which constitutively expresses indoleamine-2,3-dioxygenase (IDO), a molecule shown to prevent the rejection of fetus during pregnancy, has recently been described. This subset, characterized by nonadherence and CD123/CCR6 expression, exhibited sustained IDO production if exposed to interleukin (IL)-10. In the present work, we generated human nonadherent, CD123/CCR6 DCs secreting IL-10. METHODS:Monocytes were separated by plastic adherence and differentiated to DCs in the presecence of IL-3 and IL-4. Expression of IDO was determined by reverse-transcriptase polymerase chain reaction and enzyme activity by reverse-phased high-performance liquid chromatography. Mixed lymphocyte cultures were performed with allogeneic nylon wool-purified T-cells. RESULTS:Contradicting previous findings, CD123+/CCR6+ DCs did not express IDO. Maturation of these cells with inducer-cytokines up-regulated IDO, but the allogeneic T-cell stimulatory capacity of these DCs was even stronger than that of immature IDO DCs, and chemical abrogation of IDO activity did not increase T-cell proliferation. In parallel, we generated mature IDO DCs, but these cells also did not induce stronger T-cell stimulation than their IDO counterpart. CONCLUSIONS:In conclusion, CD123/CCR6 DCs do not constitutively express IDO and "induced" IDO DCs, even coexpressing anti-inflammatory IL-10, do not suppress allogeneic T-cell responses.

journal_name

Transplantation

journal_title

Transplantation

authors

Löb S,Ebner S,Wagner S,Weinreich J,Schäfer R,Königsrainer A

doi

10.1097/01.tp.0000251646.09702.ec

subject

Has Abstract

pub_date

2007-02-27 00:00:00

pages

468-73

issue

4

eissn

0041-1337

issn

1534-6080

pii

00007890-200702270-00015

journal_volume

83

pub_type

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