Resting Regulatory CD4 T Cells A Site of HIV Persistence in Patients on Long-Term Effective Antiretroviral Therapy 英文参考文献.docVIP

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Resting Regulatory CD4 T Cells A Site of HIV Persistence in Patients on Long-Term Effective Antiretroviral Therapy 英文参考文献.doc

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Resting Regulatory CD4 T Cells A Site of HIV Persistence in Patients on Long-Term Effective Antiretroviral Therapy 英文参考文献

RestingRegulatoryCD4TCells:ASiteofHIVPersistence inPatientsonLong-TermEffectiveAntiretroviralTherapy Tu-AnhTran1,Marie-GhislainedeGoe¨rdeHerve1,HouriaHendel-Chavez2,BamoryDembele1,EmilieLe Ne′vot2,KarimAbbed2,CoraliePallier4,Ce′cileGoujard1,3,JacquesGasnault1,3,Jean-Franc?ois Delfraissy1,3,Anne-MarieBalazuc5,YassineTaoufik1,2* 1INSERM U802, Universite′ Paris 11, LeKremlinBice?tre,France, 2Unite′ d’Immunologie Biologique,Assistance Publique-Ho?pitauxde Paris, Ho?pitalBice?tre,Le Kremlin- Bice?tre,France,3ServicedeMe′decine Interne,AssistancePublique-Ho?pitauxdeParis,Ho?pitalBice?tre,LeKremlin-Bice?tre,France,4LaboratoiredeVirologie,Assistance Publique-Ho?pitauxdeParis,Ho?pitalBice?tre,LeKremlin-Bice?tre,France,5InstitutPasteur,Paris,France Abstract Background: In HIV-infected patients on long-term HAART, virus persistence in resting long-lived CD4 T cells is a major barriertocuringtheinfection.Cellquiescence,byfavouringHIVlatency,reducestheriskofrecognitionandcelldestruction by cytotoxic lymphocytes. Several cell-activation-based approaches have been proposed to disrupt cell quiescence and + + + thenviruslatency,buttheseapproacheshavenoteradicatedthevirus.CD4 CD25 regulatoryTcells(Tregs)areaCD4 T- cellsubsetwithparticularactivationproperties.Weinvestigatedtheroleofthesecellsinviruspersistenceinpatientson long-termHAART. Methodology/Principal Findings: We found evidence of infection of resting Tregs (HLADR2CD692CD25hiFoxP3+CD4+ T cells)purifiedfrompatientsonprolongedHAART.HIVDNAharbouringcellsappearmoreabundantintheTregsubsetthan innon-Tregs.Thehalf-lifeoftheTregreservoirwasestimatedat20months.SinceTregsfrompatientsonprolongedHAART showedhyporesponsivenesstocellactivationandinhibitionofHIV-specificcytotoxicTlymphocyte-relatedfunctionsupon activation,therapeuticstargetingcellquiescencetoinducevirusexpressionmaynotbeappropriateforpurgingtheTreg reservoir. Conclusions:OurresultsidentifyTregsasaparticularcompartmentwithinthelatentreservoirthatmayrequireaspecif