International Immunology Advance Access originally published online on February 14, 2005
International Immunology 2005 17(4):351-363; doi:10.1093/intimm/dxh215
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Mycophenolic acid-treated human dendritic cells have a mature migratory phenotype and inhibit allogeneic responses via direct and indirect pathways
1 JE 2448, Cellules Dendritiques et Greffes, IFR 135, Imagerie et exploration fonctionnelles, Université François Rabelais, 2 bis Bd Tonnelle, 37032 Tours, France
2 Etablissement Français du Sang, Centre Atlantique, Tours, France
3 UFR des Sciences Pharmaceutiques, 31 Avenue Monge, 32200 Tours, France
Correspondence to: Y. Lebranchu; E-mail: lebranchu{at}med.univ-tours.fr
Immature dendritic cells (DCs) can induce T-cell hyporesponsiveness, thus interfering with the process of DC maturation in a pro-inflammatory context, may therefore provide a novel approach to inducing allograft tolerance. We have studied the effects of mycophenolic acid (MPA), an immunosuppressive agent currently used in transplantation, using an in vitro model of a mixed human DC/alloreactive CD4+ T lymphocyte culture. DCs differentiated from monocytes were exposed to MPA during maturation. MPA treatment affected the maturation of DCs, and this was reflected both in the impairment of the up-regulation of co-stimulatory molecule expression and the maintained endocytic capacity. However, MPA-DCs exhibited a distinctive microscopic morphology and secreted IL-10 and so could no longer be regarded as immature DC. Moreover, MPA-DCs had a mature phenotype for chemokine receptor expression, exhibiting down-regulation of CCR5 and up-regulation of CCR7. Interestingly, the abilities of the MPA-DCs to induce CD4+ T-cell proliferation in response to alloantigens was impaired not only via direct but also via indirect pathways. The maintenance of endocytosis and the inhibition of syngeneic T-cell activation suggest that these cells could have a potential role to avoid chronic rejection. All these characteristics suggest that MPA-DCs may be used in cell therapy to induce allograft tolerance.
Keywords: Cell therapy, Immunosuppressive agent, Tolerance, Transplantation
Transmitting editor: E. Vivier
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