《调节性T细胞》课件课件.pptVIP

CD4+CD25+regulatoryTcell

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MilestoneforTregcelldiscovery2.

AspecialCD4+TcellTregisaspecialCD4+TcellMostCD4+TcellsbelongtoTh1orTh2But5%--10%ofCD4+TcellsbelongtoneitheronewhichiscalledCD4+CD25+regulatorTcells3.

HeterogeneousgroupsofTregcellsNaturalTregcells(nTreg)InducedTregcellsiTregTh3cells(TGF-?)Tr1(IL-10)RegulatoryCD8+TcellRegulatoryNKTcellCD4-CD8-(DN)Tcells???Tcells4.

HowTregsarise??THYMUS(nTreg,CD25+;SUPPRESSAUTOIMUNITY)PERIPHERAL(iTreg,Tr1,Th3;DAMPENIMMUNEREACTIONSTOPATHOGENS)5.

DevelopmentofTreginthymus6.

DiversificationofCD4TCellLineages7.

SearchingforthemarkersofTregcells8.

MolecularMarkerFunctionCD4+-BindsMHCclassII-ExpressedonThcellsCD25+-ExpressedonmostTregcellsCD3+-EnsuresexpressionofTCRGITR-Negativesignaling-RequiredforsurvivalCTLA-4-BindsCD80/CD86-AntagonizeseffectsofCD28toCD80/86CCR7-MediatesmigrationofTregcellsbacktolymphnodesFoxp3-RequiredfordifferentiationandfunctionofTregcells9.

NOTE!TherearenoknowncellsurfacemoleculesthatuniquelydistinguishtheCD4+TregcellsfromconventionalactivatedCD4+Tcells!CD25CTLA-4GITRCD4+CD25+RegulatoryTcell10.

.FOXP3isthespecificmarker-mediatorofthegeneticprogramgoverningCD25+CD4+Tregcelldevelopmentandfunction11.

.FOXP3ControlsRegulatoryTCellFunctionthroughCooperationwithNFATByswitchingtranscriptionalpartners[Fos-Jun(AP-1)vs.FOXP3],NFATconvertstheTcellactivationprogramintothesuppressorprogramofTregs12.

.ControlofTregfunctionbyFoxP313.

TregactivationandproliferationActivatedbycontactwithDC(evenimmature!).14.

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TraffickingandlocalizationofTregsBlood,lymphoidorgans;varietyofhomingreceptorsnecessaryformigrationtolymphnodes,sitesofinflammation.18.

TregcellmediatedphenomenonBystandersuppressionSuppressiveactivityofTregcellsrequirestheirprioractivationthroughtheirTcellrece