Analysis of Mycobacterium tuberculosis-Specific CD8 T-Cells in Patients with Active Tuberculosis and in Individuals with Latent Infection 英文参考文献.docVIP

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Analysis of Mycobacterium tuberculosis-Specific CD8 T-Cells in Patients with Active Tuberculosis and in Individuals with Latent Infection 英文参考文献.doc

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Analysis of Mycobacterium tuberculosis-Specific CD8 T-Cells in Patients with Active Tuberculosis and in Individuals with Latent Infection 英文参考文献

AnalysisofMycobacteriumtuberculosis-SpecificCD8T- CellsinPatientswithActiveTuberculosisandin IndividualswithLatentInfection NadiaCaccamo1*,GiulianaGuggino1,SerenaMeraviglia1,GiuseppeGelsomino1,PaolaDiCarlo2 ,Lucina Titone2,MarialuisaBocchino3,DomenicoGalati3,AlessandroMatarese3,JanNouta4,MichelR.Klein5, AlfredoSalerno1,AlessandroSanduzzi3,FrancescoDieli1.,TomH.M.Ottenhoff4. 1Dipartimento di Biopatologia e Metodologie Biomediche, Universita` di Palermo, Palermo, Italy, 2Dipartimento di Medicina Clinica e delle Patologie Emergenti, Universita`diPalermo,Palermo,Italy,3TBInfectionScreeningUnit,DepartmentofClinicalandExperimentalMedicine,UniversityofNaples‘‘FedericoII’’,MonaldiHospital, Naples, Italy, 4Department of Immunohematology Blood Transfusion and Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands,5NationalInstituteofPublicHealthandtheEnvironment,Bilthoven,TheNetherlands Abstract CD8T-cellscontributetocontrolofMycobacteriumtuberculosisinfection,butlittleisknownaboutthequalityoftheCD8T- cell response in subjects with latent infection and in patients with active tuberculosis disease. CD8 T-cells recognizing epitopesfrom6differentproteinsofMycobacteriumtuberculosisweredetectedbytetramerstaining.Intracellularcytokines stainingforspecificproductionofIFN-candIL-2wasperformed,complementedbyphenotypingofmemorymarkerson antigen-specificCD8T-cells.Theex-vivofrequenciesoftetramer-specificCD8T-cellsintuberculouspatientsbeforetherapy werelowerthaninsubjectswithlatentinfection,butincreasedatfourmonthsaftertherapytocomparablepercentages detected in subjects with latent infection. The majority of CD8 T-cells from subjects with latent infection expressed a terminally-differentiated phenotype (CD45RA+CCR72). In contrast, tuberculous patients had only 35% of antigen-specific CD8T-cellsexpressingthisphenotype,whilecontaininghigherproportionsofcellswithaneffectormemory-andacentral memory-like phenotype, and which did not change significantly