Reactivation of Latent Tuberculosis in Cynomolgus Macaques Infected with SIV Is Associated with Early Peripheral T Cell Depletion and Not Virus Load 英文参考文献.docVIP

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Reactivation of Latent Tuberculosis in Cynomolgus Macaques Infected with SIV Is Associated with Early Peripheral T Cell Depletion and Not Virus Load 英文参考文献.doc

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Reactivation of Latent Tuberculosis in Cynomolgus Macaques Infected with SIV Is Associated with Early Peripheral T Cell Depletion and Not Virus Load 英文参考文献

ReactivationofLatentTuberculosisinCynomolgus MacaquesInfectedwithSIVIsAssociatedwithEarly PeripheralTCellDepletionandNotVirusLoad CollinR.Diedrich1.,JoshuaT.Mattila1.,EdwinKlein2,ChrisJanssen2,JiayaoPhuah1,TimothyJ. Sturgeon3,RonaldC.Montelaro3,PhilanaLingLin4,JoAnneL.Flynn1* 1Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America, 2Division of LaboratoryAnimalResources,UniversityofPittsburghSchoolofMedicine,Pittsburgh,Pennsylvania,UnitedStatesofAmerica,3CenterforVaccineResearch,Universityof Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America, 4Department of Pediatrics, Children’s Hospital of Pittsburgh of the University of PittsburghMedicalCenter,Pittsburgh,Pennsylvania,UnitedStatesofAmerica Abstract HIV-infectedindividualswithlatentMycobacteriumtuberculosis(Mtb)infectionareatsignificantlygreaterriskofreactivation tuberculosis(TB)thanHIV-negativeindividualswithlatentTB,evenwhileCD4Tcellnumbersarewellpreserved.Factors underlying high rates of reactivation are poorly understood and investigative tools are limited. We used cynomolgus macaqueswithlatentTBco-infectedwithSIVmac251todevelopthefirstanimalmodelofreactivatedTBinHIV-infected humanstobetterexplorethesefactors.AlllatentanimalsdevelopedreactivatedTBfollowingSIVinfection,withavariable timetoreactivation(upto11monthspost-SIV).Reactivationwasindependentofvirusloadbutcorrelatedwithdepletionof peripheral Tcellsduring acuteSIV infection.Animalsexperiencing reactivation earlyafterSIV infection(,17weeks)had fewerCD4TcellsintheperipheryandairwaysthananimalsreactivatinginlaterphasesofSIVinfection.Co-infectedanimals hadfewerTcellsininvolvedlungsthanSIV-negativeanimalswithactiveTBdespitesimilarTcellnumbersindraininglymph nodes. Granulomas from these animals demonstrated histopathologic characteristics consistent with a chronically active diseaseprocess.TheseresultssuggestinitialTcelldepletionmaystron