Direct Ex-Vivo Evaluation of Pneumococcal Specific T-Cells in Healthy Adults 英文参考文献.docVIP

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Direct Ex-Vivo Evaluation of Pneumococcal Specific T-Cells in Healthy Adults 英文参考文献.doc

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Direct Ex-Vivo Evaluation of Pneumococcal Specific T-Cells in Healthy Adults 英文参考文献

DirectEx-VivoEvaluationofPneumococcalSpecific T-CellsinHealthyAdults AamirAslam1,HelenChapel2,GrahamOgg1* 1MRCHumanImmunologyUnit,OxfordNIHRBiomedicalResearchCentre,Weatherall InstituteofMolecularMedicine,UniversityofOxford,Oxford,UnitedKingdom, 2ClinicalImmunologyUnit,NuffieldDepartmentofMedicine,UniversityofOxford,Oxford,UnitedKingdom Abstract Streptococcus pneumoniae is an encapsulated bacterium that causes significant global morbidity and mortality. The nasopharynxes of children are believed to be the natural reservoir of pneumococcus and by adulthood nasopharyngeal carriageisinfrequent;suchinfrequencymaybeduetodemonstrablepneumococcalspecificTandB-cellresponses.HLA Class 2 tetrameric complexes have been used to characterise antigen specific T-cell responses in a variety of models of infection. We therefore sought to determine the frequency and phenotype of pneumococcal specific T-cells, using a novel HLA-DRB1*1501 tetramer complex incorporating a recently defined T-cell epitope derived from the conserved pneumococcal serine/threonine kinase (StkP). We were able to detect direct ex-vivo StkP446–60-tetramer binding in HLA- DRB1*1501 adults.TheseStkP -tetramer binding T-cellshadincreased CD38expressionandwereenriched inCCR7- 446–60 CD45RA+expressionindicatingrecentandon-goingactivationanddifferentiation.Furthermore,theseStkP446–60-tetramer bindingT-cellsdemonstratedrapideffectorfunctionbysecretinginterferon-gammaonstimulationwithrecombinantStkP. This is the first study to directly enumerate and characterise pneumococcal specific T-cells using HLA class 2 tetrameric complexes.Wefoundthatex-vivopneumococcal-specificTcellsweredetectableinhealthyadultsandthattheywereenriched withcellsurfacemarkersassociatedwithrecentantigenexposureandlaterstagesofantigen-drivendifferentiation.Itislikely that these activated pneumococcal specific T-cells reflect recent immunostimulatory pneumococcal exposure in the nasopharynxanditispossiblethattheymaybepreventingsubsequentcol