Are indoleamine-2,3-dioxygenase producing human dendritic cells a tool for suppression of allogeneic T-cell responses?
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.
Löb
Stefan
S
Department of General-, Visceral- and Transplantation Surgery, Eberhard Karls University, Tübingen, Germany. stefan.loeb@med.uni-tuebingen.de
Ebner
Susanne
S
Wagner
Silvia
S
Weinreich
Jürgen
J
Schäfer
Richard
R
Königsrainer
Alfred
A
D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis* / Q000235:genetics; D016753:Interleukin-10 / Q000378:metabolism; D007377:Interleukin-3 / Q000494:pharmacology; D053650:Interleukin-3 Receptor alpha Subunit / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D010641:Phenotype; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
C106311:CCR6 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007377:Interleukin-3; D053650:Interleukin-3 Receptor alpha Subunit; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D016753:Interleukin-10