Antigen Load and Viral Sequence Diversification Determine the Functional Profile of HIV-1–Specific CD8+ T Cells 英文参考文献.docVIP

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Antigen Load and Viral Sequence Diversification Determine the Functional Profile of HIV-1–Specific CD8+ T Cells 英文参考文献.doc

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AntigenLoadandViralSequenceDiversificationDeterminetheFunctionalProfileofHIV-1–SpecificCD8TCells英文参考文献

o PL SMEDICINE AntigenLoadandViralSequenceDiversification DeterminetheFunctionalProfileof HIV-1–SpecificCD8tTCells Hendrik Streeck1,Zabrina L.Brumme1,Michael Anastario2,Kristin W. Cohen1,Jonathan S.Jolin1,Angela Meier1, Chanson J.Brumme1,Eric S.Rosenberg1,Galit Alter1,Todd M.Allen1,Bruce D.Walker1,3,Marcus Altfeld1* 1PartnersAIDSResearchCenter,InfectiousDiseaseUnit,MassachusettsGeneralHospitalandDivisionofAIDS,HarvardMedicalSchool,Boston,Massachusetts,UnitedStates of America, 2 Center for Disaster and Humanitarian Assistance Medicine, Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences,Bethesda,Maryland,UnitedStatesofAmerica,3HowardHughesMedicalInstitute,ChevyChase,Maryland,UnitedStatesofAmerica Funding:Thisstudywassupported bytheNationalInstitutesofHealth (RO1AI50429)andAcuteInfection EarlyDiseaseResearchNetwork(U01 AI052403).Inaddition,HSis ABSTRACT Background supportedbytheDeutscher Virus-specific CD8t T lymphocytes play a key role in the initial reduction of peak viremia duringacuteviralinfections,butdisplaysignsofincreasingdysfunctionandexhaustionunder conditionsofchronicantigenpersistence.Ithasbeensuggestedthatvirus-specificCD8t Tcells with a ‘‘polyfunctional’’ profile, defined by the capacity to secrete multiple cytokines or chemokines,aremostcompetentincontrollingviralreplicationinchronicHIV-1infection.We usedHIV-1infectionasamodelofchronicpersistentviralinfectiontoinvestigatetheprocess of exhaustion and dysfunction of virus-specific CD8t T cell responses on the single-epitope levelovertime,startinginprimaryHIV-1infection. AkademischerAustauschdiensts (DAAD).ZLBissupportedbya postdoctoralfellowshipfromthe CanadianInstitutesofHealth Research(CIHR).Thefundersdidnot haveanyroleinthestudydesign, datacollectionandanalysis,decision topublish,orpreparationofthe manuscript. CompetingInterests:Theauthors havedeclaredthatnocompeting interestsexist. MethodsandFindings AcademicEditor:SarahRowland- Jones,WeatherallI