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1、NIHPublicAccessAuthorManuscriptAdvDrugDelivRev.Authormanuscript;availableinPMC2008February5.NIH-PAAuthorManuscriptPublishedinfinaleditedformas:NIH-PAAuthorManuscriptNIH-PAAuthorManuscriptAdvDrugDelivRev.2008January14;60(2):91±105.doi:10.1016/j.addr.2007.08.025.AdvancementsinImmuneTolerancePi
2、ng-YingPan*,JunkoOzao,ZupingZhou,andShu-HsiaChen*DepartmentofGeneandCellMedicine,MountSinaiSchoolofMedicine,NewYork,NY,10029,USAAbstractInrecentyears,considerableattentionhasbeengiventoimmunetoleranceanditspotentialclinicalapplicationsforthetreatmentofcancersandautoimmunediseases,andthepreve
3、ntionofallograftrejectionandgraft-versus-hostdiseases.Advancesinourunderstandingoftheunderlyingmechanismsofestablishmentandmaintenanceofimmunetoleranceinvariousexperimentalsettingsandanimalmodels,andinourabilitytomanipulatethedevelopmentofvariousimmunetolerogeniccellsinvitroandinvivo,havegen
4、eratedsignificantmomentumforthefieldofcell-basedtolerogenictherapy.Thisreviewbrieflysummarizesthemajortolerogeniccellpopulationsandtheirmechanismsofaction,whilefocusingmainlyonpotentialexploitationoftheirtolerogenicmechanismsforclinicalapplications.KeywordsImmunetolerance;cancerimmunetherapy
5、;autoimmune;Treg;MDSC;dendriticcells;GVHD1.IntroductiontoImmunetoleranceThehallmarkoftheimmunesystemistheabilitytodiscriminatebetweenselfandnon-selfantigensi.e.,itmustbeabletomaintaintolerancetoself-antigensyetbeabletomounteffectiveimmuneresponsesagainstpathogensandmalignantcells.Therelation
6、shipbetweentoleranceandimmunityisdynamicandcanbevisualizedasthetwoarmsofascale,whichmustbedelicatelybalanced.Atilttowardeithersideresultsinadversepathophysiologicalconditionsthatmayleadtodiseasemanifestations,suchasinfections,malignancies,orautoimmunity.Inordertoavoidharmfulself-reactivity,s
7、elf-tolerancewithintheT-cellrepertoireisachievedthroughcentralandperipheraltolerance.ThymiceducationconstitutesthemainprocessofcentraltoleranceinwhichthemajorityofdevelopingTcellswithstrongself-reactivityaredeleted[1–4].Afterexitingthethymus,mature
