Peripheral T Cell Cytokine Responses for Diagnosis of Active Tuberculosis 英文参考文献.docVIP

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Peripheral T Cell Cytokine Responses for Diagnosis of Active Tuberculosis 英文参考文献.doc

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Peripheral T Cell Cytokine Responses for Diagnosis of Active Tuberculosis 英文参考文献

PeripheralTCellCytokineResponsesforDiagnosisof ActiveTuberculosis JohannesNemeth1,2,Heide-MariaWinkler1,RalphH.Zwick3,CatharinaMu¨ller1,RudolfRumetshofer3, LucasBoeck4,OttoC.Burghuber3,StefanWinkler1* 1DepartmentofInternalMedicineI,DivisionofInfectiousDiseasesandTropicalMedicine,MedicalUniversityofVienna,Vienna,Austria,2DivisionofInfectiousDiseases andHospitalEpidemiology,UniversityHospitalZurich,Zurich,Switzerland,3DepartmentofRespiratoryandCriticalCareMedicine,Otto-Wagner-Hospital,Vienna,Austria, 4ClinicofPulmonaryMedicineandRespiratoryCellResearch,UniversityHospitalBasel,Basel,Switzerland Abstract Background: A test for diagnosis of active Tuberculosis (TB) from peripheral blood could tremendously improve clinical managementofpatients. Methods: Of 178 prospectively enrolled patients with possible TB, 60 patients were diagnosed with pulmonary and 27 + + patientswithextrapulmonaryTB.ThefrequenciesofMycobacteriumtuberculosis(MTB)specificCD4 TcellsandCD8 Tcells producing cytokines were assessed using overnight stimulation with purified protein derivate (PPD) or early secretory antigenictarget(ESAT)-6,respectively. Results: Among patients with active TB, an increased type 1 cytokine profile consisting of mainly CD4+ T cell derived interferon (IFN)-c was detectable. Despite contributing to the cytokine profile as a whole, the independent diagnostic performanceofonecytokineproducingTcellsaswellaspolyfunctionalTcellswaspoor.IFN-c/Interleukin(IL)-2cytokine ratiosdiscriminatedbestbetweenactiveTBandotherdiseases. Conclusion: T cells producing one cytokine and polyfunctional T cells have a limited role in diagnosis of active TB. The significantshiftfroma‘‘memorytype’’toan‘‘effectortype’’cytokineprofilemaybeusefulforfurtherdevelopmentofa rapidimmune-diagnostictoolforactiveTB. Citation:NemethJ,WinklerH-M,ZwickRH,Mu¨llerC,RumetshoferR,etal.(2012)PeripheralTCellCytokineResponsesforDiagnosisofActiveTuberculosis.PLoS ONE7(4):e35290.doi:10.1371/journal.pone.0035290 Editor:A