Attenuated Disease in SIV-Infected Macaques Treated with a Monoclonal Antibody against FasL英文文献资料.docVIP

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Attenuated Disease in SIV-Infected Macaques Treated with a Monoclonal Antibody against FasL英文文献资料.doc

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Attenuated Disease in SIV-Infected Macaques Treated with a Monoclonal Antibody against FasL英文文献资料

HindawiPublishingCorporation ClinicalandDevelopmentalImmunology Volume2007,ArticleID93462,9pages doi:10.1155/2007/93462 ResearchArticle AttenuatedDiseaseinSIV-InfectedMacaquesTreatedwith aMonoclonalAntibodyagainstFasL MariaS.Salvato,1C.CameronYin,2,3HideoYagita,4ToshihiroMaeda,5KoOkumura,5 IliaTikhonov,1andC.DavidPauza1 1 2 InstituteofHumanVirology,UniversityofMarylandBiotechnologyInstitute,Baltimore,MD21201,USA DepartmentofPathologyandLaboratoryMedicine,SchoolofMedicineandPublicHealth,UniversityofWisconsin, Madison,WI53705,USA 3 4 5 DepartmentofHematopathology,MDAndersonCancerCenter,UniversityofTexas,Houston,TX77030,USA DepartmentofImmunology,JuntendoUniversitySchoolofMedicine,Tokyo113-8421,Japan TheChemo-SeroTherapeuticResearchInstitute(Kaketsuken),Kumamoto860-8568,Japan CorrespondenceshouldbeaddressedtoC.DavidPauza,pauza@ Received8October2007;Accepted31October2007 RecommendedbyEthanM.Shevach AcuteSIVmacinfectioninmacaquesisaccompaniedbyhighlevelsofplasmaviremiathatdeclinewiththeappearanceofviralim- munityandisamodelforacuteHIVdiseaseinman.Despitespeci?cimmuneresponses,thevirusestablishesachronic,persistent infection.ThedestructionofCD4+andCD4?lymphocytesubsetsinmacaquescontributestoviralpersistenceandsuggeststhe importanceofmechanismsfordepletingbothinfectedanduninfected(bystander)cells.BystandercellkillingcanoccurwhenFasL bindstheFasreceptoronactivatedlymphocytes,whichincludeTandBcellsubpopulationsthatarerespondingtotheinfection. Destructionofspeci?cimmunecellscouldbeanimportantmechanismforbluntingviralimmunityandestablishingpersistent infectionwithchronicdisease.WeinhibitedtheFaspathwayinvivowithamonoclonalantibodyagainstFasL(RNOK203).Here weshowthattreatmentwithanti-FasLreducedcelldeathincirculatingTandBcells,increasedCTLandantibodyresponsesto viralproteins,andloweredthesetpointviremia.ByblockingFasLduringonlythe?rstfewweeksafterinfection,weattenuated SIVmacdiseaseandincreasedthelifespanforinfectedandtreatedmacaques. Copyright?2007MariaS.Salvatoetal. This