Both Maturation and Survival of Human Dendritic Cells are Impaired in the Presence of AnergicSuppressor T Cells英文文献资料.docVIP

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Both Maturation and Survival of Human Dendritic Cells are Impaired in the Presence of AnergicSuppressor T Cells英文文献资料.doc

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Both Maturation and Survival of Human Dendritic Cells are Impaired in the Presence of AnergicSuppressor T Cells英文文献资料

ClinicalDevelopmentalImmunology,March2003,Vol.10(1),pp.61–65 BothMaturationandSurvivalofHumanDendriticCellsare ImpairedinthePresenceofAnergic/SuppressorTCells L.FRASCAa,*,C.SCOTTA`a,G.LOMBARDIbandE.PICCOLELLAa aDepartmentofCellDevelopmentandBiology,“LaSapienza”University,ViadeiSardi,70-00185,Rome,Italy;bDepartmentofImmunology,Imperial CollegeofMedicine,HammersmithHospital,W120NN,London,UK Tcellsuppressionisawellestablishedphenomenon,butthemechanismsinvolvedarestillamatterof debate.MouseanergicTcellswereshowntosuppressresponderTcellactivationbyinhibitingthe antigenpresentingfunctionofDC.Inthepresentworkwestudiedtheeffectsofco-culturinghuman t anergicCD4 Tcellswithautologousdendriticcells(DC)atdifferentstagesofmaturation.EitherDC maturation or survival, depending on whether immature or mature DC where used as APC, was impairedinthepresenceofanergiccells.Indeed,MHCandcostimulatorymoleculeup-regulationwas inhibitedinimmatureDC,whereasapoptoticphenomenawerefavoredinmatureDCandconsequently in responder T cells. Defective ligation of CD40 by CD40L (CD154) was responsible for CD95- mediatedandspontaneousapoptosisofDCaswellasforafailureoftheirmaturationprocess.These ?ndingsindicatethatlackofactivationofCD40onDCbyCD40L-defectiveanergiccellsmightbethe primaryeventinvolvedinTcellsuppressionandsupporttheroleofCD40signalinginregulatingboth activationandsurvivalofDC. Keywords: Anergy;CD40–CD40Linteraction;DC;Tcellsuppression INTRODUCTION Frascaetal.,1997).Herewewantedtoanalyzethesame phenomenoninamorephysiologicalconditionusingDC asAPC.CloneF17,HA307-19-speci?candDRB1*1101- restricted,wasinparteitheranergized(Frascaetal. ,1997) oractivatedwithPMAtI.Figure1showsitssuppressive activity on responder cells of the same clone (anergic/responder cells ratio 3:1), in the presence of T cells can transfer tolerance from a tolerant to a na?¨ve host(Gerson,1975;Charltonetal.,1994)aphenomenon referred to as “infectious tolerance” (Zhai and Kupie- Weglinski, 1999). We have shown that hu