FOXP3 Expression Is Upregulated in CD4+T Cells in Progressive HIV-1 Infection and Is a Marker of Disease Severity 英文参考文献.docVIP

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FOXP3 Expression Is Upregulated in CD4+T Cells in Progressive HIV-1 Infection and Is a Marker of Disease Severity 英文参考文献.doc

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FOXP3ExpressionIsUpregulatedinCD4TCellsinProgressiveHIV-1InfectionandIsaMarkerofDiseaseSeverity英文参考文献

FOXP3ExpressionIsUpregulatedinCD4+TCellsin ProgressiveHIV-1InfectionandIsaMarkerofDisease Severity MelindaS.Suchard1,2,4*,ElizabethMayne1,4,VictoriaA.Green1,3,4,SharonShalekoff4,SamanthaL. Donninger4,WendyS.Stevens1,CliveM.Gray4,CarolineT.Tiemessen4 1HaematologyandMolecularMedicine,NationalHealthLaboratoryServiceandUniversityoftheWitwatersrand,Johannesburg,SouthAfrica,2Microbiology,National HealthLaboratoryServiceandUniversityoftheWitwatersrand,Johannesburg,SouthAfrica,3DepartmentofBiologyandBiochemistry,UniversityofBath,Bath,United Kingdom,4AIDSVirusResearchUnit,NationalInstituteforCommunicableDisease,Johannesburg,SouthAfrica Abstract Background: Understanding the role of different classes of T cells during HIV infection is critical to determining which responsescorrelatewithprotectiveimmunity.Todate,itisunclearwhetheralterationsinregulatoryTcell(Treg)function arecontributorytoprogressionofHIVinfection. Methodology:FOXP3expressionwasmeasuredbybothqRT-PCRandbyflowcytometryinHIV-infectedindividualsand uninfectedcontrolstogetherwithexpressionofCD25,GITRandCTLA-4.Culturedperipheralbloodmononuclearcellswere stimulatedwithanti-CD3andcellproliferationwasassessedbyCFSEdilution. PrincipalFindings:HIVinfectedindividualshadsignificantlyhigherfrequenciesofCD4+FOXP3+Tcells(medianof8.11%; range 1.33%–26.27%) than healthy controls (median 3.72%; range 1.3–7.5%; P=0.002), despite having lower absolute countsofCD4 FOXP3+Tcells.TherewasasignificantpositivecorrelationbetweenthefrequencyofCD4 FOXP3+Tcellsand viralload(rho=0.593P=0.003)andasignificantnegativecorrelationwithCD4count(rho=20.423P=0.044).48%ofour patientshadCD4countsbelow200cells/mlandthesepatientsshowedamarkedelevationofFOXP3percentage(median 10%range4.07%–26.27%).AssessingthemechanismofincreasedFOXP3frequency,wefoundthatthehighFOXP3levels notedinHIVinfectedindividualsdroppedrapidlyinunstimulatedcultureconditionsbutcouldberestimulatedbyTcell receptor stimulation. This suggests that the high FOXP3 expression in HIV