Mtb-Specific CD27low CD4 T Cells as Markers of Lung Tissue Destruction during Pulmonary Tuberculosis in Humans 英文参考文献.docVIP

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Mtb-Specific CD27low CD4 T Cells as Markers of Lung Tissue Destruction during Pulmonary Tuberculosis in Humans 英文参考文献.doc

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Mtb-Specific CD27low CD4 T Cells as Markers of Lung Tissue Destruction during Pulmonary Tuberculosis in Humans 英文参考文献

Mtb-SpecificCD27low CD4TCellsasMarkersofLung TissueDestructionduringPulmonaryTuberculosisin Humans IrinaYuNikitina1,NatalyaA.Kondratuk1,GeorgeA.Kosmiadi1,RasulB.Amansahedov2, IrinaA.Vasilyeva3.,VitalyV.Ganusov4,5.,IrinaV.Lyadova1*. 1Department of Immunology, Central Tuberculosis Research Institute, Moscow, Russia, 2Department of Radiology, Central Tuberculosis Research Institute, Moscow, Russia, 3Department of Phtisiology, Central Tuberculosis Research Institute, Moscow, Russia, 4Department of Microbiology, University of Tennessee, Knoxville, Tennessee,UnitedStatesofAmerica,5NationalInstituteforMathematicalandBiologicalSynthesis(NIMBioS),Knoxville,Tennessee,UnitedStatesofAmerica Abstract Background:EffectorCD4Tcellsrepresentakeycomponentofthehost’santi-tuberculosisimmunedefense.Successful differentiationandfunctioningofeffectorlymphocytesprotectsthehostagainstsevereM.tuberculosis(Mtb)infection.On theotherhand,effectorTcelldifferentiationdependsondiseaseseverity/activity,asTcellresponsesaredrivenbyantigenic andinflammatorystimulireleasedduringinfection.Thus,tuberculosis(TB)progressionandthedegreeofeffectorCD4Tcell differentiationareinterrelated,buttherelationshipsarecomplexandnotwellunderstood.Wehaveanalyzedanassociation betweenthedegreeofMtb-specificCD4Tcelldifferentiationandseverity/activityofpulmonaryTBinfection. Methodology/PrincipalFindings:ThedegreeofCD4Tcelldifferentiationwasassessedbymeasuringthepercentagesof + highly differentiated CD27low cells within a population of Mtb- specific CD4 T lymphocytes (‘‘CD27lowIFN-c ’’ cells). The percentagesofCD27lowIFN-c+cellswerelowinhealthydonors(median,33.1%)andTBcontacts(21.8%)butincreasedinTB + patients(47.3%,p,0.0005).Withinthegroupofpatients,thepercentagesofCD27lowIFN-c cellswereuniformlyhighinthe + lungs(.76%),butvariedinblood(12–92%).ThemajorcorrelatefortheaccumulationofCD27lowIFN-c cellsinbloodwas + lungdestruction(r=0.65,p=2.761027).Acutoffof47%ofCD27lowIFN-c cellsdiscriminatedpatientswithhigh