Prolonged Graft Survival in Older Recipient Mice Is Determined by Impaired Effector T-Cell but Intact Regulatory T-Cell Responses 英文参考文献.docVIP

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Prolonged Graft Survival in Older Recipient Mice Is Determined by Impaired Effector T-Cell but Intact Regulatory T-Cell Responses 英文参考文献.doc

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Prolonged Graft Survival in Older Recipient Mice Is Determined by Impaired Effector T-Cell but Intact Regulatory T-Cell Responses 英文参考文献

ProlongedGraftSurvivalinOlderRecipientMiceIs DeterminedbyImpairedEffectorT-CellbutIntact RegulatoryT-CellResponses ChristianDenecke1¤,DamanpreetSinghBedi1,XupengGe1,IreneKyung-eunKim1,AnkeJurisch1 ,Anne Weiland1,AntjeHabicht2,XianC.Li3,StefanG.Tullius1* 1DivisionofTransplantSurgeryandTransplantSurgeryResearchLaboratory,BrighamandWomen’sHospital,HarvardMedicalSchool,Boston,Massachusetts,United StatesofAmerica,2TransplantationResearchCenter,BrighamandWomen’sHospitalandChildren’sHospitalofBoston,Boston,Massachusetts,UnitedStatesofAmerica, 3TransplantResearchCenter,BethIsraelDeaconessMedicalCenter,HarvardMedicalSchool,Boston,Massachusetts,UnitedStatesofAmerica Abstract Elderly organ transplant recipients represent afast growing segment of patients on thewaiting list. Weexamined age- dependent CD4+ T-cell functions in a wild-type (WT) and a transgenic mouse transplant model and analyzed the suppressive function of old regulatory T-cells. We found that splenocytes of na?¨ve old B6 mice contained significantly + higherfrequenciesofT-cellswithaneffector/memoryphenotype(CD4 CD44highCD62Llow).However,in-vitroproliferation (MLR) and IFNc-production (ELISPOT) were markedly reduced with increasing age. Likewise, skin graft rejection was T-cells + + significantly delayed in older recipients and fewer graft infiltrating CD4 T-cells were observed. Old CD4 demonstrated asignificant impaired responsiveness asindicated by diminished proliferation andactivation. Incontrast, old alloantigen-specific CD4 CD25 FoxP3+ T-cells demonstrated a dose-dependent well-preserved suppressor function. Next,weexaminedcharacteristicsof18-montholdalloreactiveT-cellsinatransgenicadoptivetransfermodel.Adoptively transferredoldT-cellsproliferatedsignificantlylessinresponsetoantigen.Skingraftrejectionwassignificantlydelayedin olderrecipients,andgraftinfiltratingcellswerereduced.Insummary,advancedrecipientagewasassociatedwithdelayed + + acuterejectionandimpairedCD4 T-cellfunctionandproliferationwhile