Donor‐derived, tolerogenic dendritic cells suppress immune rejection in the indirect allosensitization‐dominant setting of corneal transplantation

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: indirect pathway;    direct pathway;    tolerance;    regulatory DC;   

DOI  :  10.1189/jlb.1011500

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Significantinteresthasbeenfocusedontheuseofexvivo‐manipulatedDCstooptimallyinducetransplanttoleranceandpromoteallograftsurvival.Althoughitisunderstoodthatdonor‐derived,tolerogenicDCssuppressthedirectpathwayofallosensitization,whethersuchDCscansimilarlysuppresstheindirectpathwayremainsunclear.Wethereforeusedthemurinemodelofcornealtransplantationtoaddressthis,astheseallograftsarerejectedinanindirectpathway‐dominantmanner.Interestingly,recipientsadministeredwithdonorbonemarrow‐derivedDCregs,generatedviaculturingwithGM‐CSF,IL‐10,andTGF‐β1,significantlyprolongedsurvivalofcornealallografts.Correspondingly,theserecipientsdemonstratedapotentreductioninthefrequencyofindirectlyallosensitizedTcells,asdeterminedbyELISPOT.ExaminationofDCregsrelativetomDCsoriDCsshowedaresistancetoup‐regulationofMHC‐IIandcostimulatorymolecules,aswellasanimpairedcapacitytostimulateMLRs.Invivo,DCregadministrationincorneal‐allograftedrecipientsledtoinhibitionofCD4+IFN‐γ+TcellfrequenciesandanassociatedincreaseinFoxp3expressionintheTregcompartment.Weconcludethatdonor‐derived,tolerogenicDCssignificantlysuppresstheindirectpathway,therebyidentifyinganovelregulatorymechanismforthesecellsintransplantation...

【 授权许可】

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