A Role for the Chemokine RANTES in Regulating CD8 T Cell Responses during Chronic Viral Infection 英文参考文献.docVIP

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A Role for the Chemokine RANTES in Regulating CD8 T Cell Responses during Chronic Viral Infection 英文参考文献.doc

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A Role for the Chemokine RANTES in Regulating CD8 T Cell Responses during Chronic Viral Infection 英文参考文献

ARolefortheChemokineRANTESinRegulatingCD8T CellResponsesduringChronicViralInfection AlisonCrawford1,JillMarieAngelosanto1,KimLynnNadwodny2,ShawnD.Blackburn1,E.JohnWherry1* 1Department of Microbiology and Institute for Immunology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America, 2GlaxoSmithKline,DepartmentofSafetyAssessment,ImmunologicToxicology,KingofPrussia,Pennsylvania,UnitedStatesofAmerica Abstract RANTES(CCL5)isachemokineexpressedbymanyhematopoieticandnon-hematopoieticcelltypesthatplaysanimportant roleinhomingandmigrationofeffectorandmemoryTcellsduringacuteinfections.TheRANTESreceptor,CCR5,isamajor targetofanti-HIVdrugsbasedonblockingviralentry.However,defectsinRANTESorRANTESreceptorsincludingCCR5can compromiseimmunitytoacuteinfectionsinanimalmodelsandleadtomoreseverediseaseinhumansinfectedwithwest Nilevirus(WNV).Incontrast,theroleoftheRANTESpathwayinregulatingTcellresponsesandimmunityduringchronic infectionremainsunclear.Inthisstudy,wedemonstrateacrucialroleforRANTESinthecontrolofsystemicchronicLCMV infection.InRANTES2/2mice,virus-specificCD8Tcellshadpoorcytokineproduction.TheseRANTES2/2CD8Tcellsalso expressedhigheramountsofinhibitoryreceptorsconsistentwithmoresevereexhaustion.Moreover,thecytotoxicabilityof CD8 T cells from RANTES2/2 mice was reduced. Consequently, viral load was higher in the absence of RANTES. The dysfunctionofTcellsintheabsenceofRANTESwasassevereasCD8TcellresponsesgeneratedintheabsenceofCD4Tcell help.OurresultsdemonstrateanimportantroleforRANTESinsustainingCD8Tcellresponsesduringasystemicchronic viralinfection. Citation:CrawfordA,AngelosantoJM,NadwodnyKL,BlackburnSD,WherryEJ(2011)ARolefortheChemokineRANTESinRegulatingCD8TCellResponses duringChronicViralInfection.PLoSPathog7(7):e1002098.doi:10.1371/journal.ppat.1002098 Editor:DanielC.Douek,NIH/NIAID,UnitedStatesofAmerica ReceivedOctober13,2010;AcceptedApril15,2011;PublishedJuly21,2011 Copyright: ? 2011 Crawford et al. This is an open-acces