Distinct Roles for FOXP3+ and FOXP3？ CD4+ T Cells in Regulating Cellular Immunity to Uncomplicated and Severe Plasmodium falciparum Malaria 英文参考文献.docVIP

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Distinct Roles for FOXP3+ and FOXP3？ CD4+ T Cells in Regulating Cellular Immunity to Uncomplicated and Severe Plasmodium falciparum Malaria 英文参考文献.doc

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DistinctRolesforFOXP3andFOXP3？CD4TCellsinRegulatingCellularImmunitytoUncomplicatedandSeverePlasmodiumfalciparumMalaria英文参考文献

DistinctRolesforFOXP3+andFOXP32 CD4+TCellsin RegulatingCellularImmunitytoUncomplicatedand SeverePlasmodiumfalciparumMalaria MichaelWalther1*,DavidJeffries1,OliviaC.Finney1,2,MadiNjie1,AugustineEbonyi1 ,Susanne Deininger1,3,EmmaLawrence1,AlfredNgwa-Amambua1,ShamanthiJayasooriya1,IanH.Cheeseman1,2, NataliaGomez-Escobar1,JosephOkebe1,DavidJ.Conway1,2,EleanorM.Riley2 1MedicalResearchCouncilLaboratories,Fajara,Banjul,TheGambia,2DepartmentofInfectiousandTropicalDiseases,LondonSchoolofHygieneandTropicalMedicine, London,UnitedKingdom,3InstituteofMedicalMicrobiology,ImmunologyandParasitology,UniversityClinicBonn,Bonn,Germany Abstract Failuretoestablishanappropriatebalancebetweenpro-andanti-inflammatoryimmuneresponsesisbelievedtocontribute topathogenesisofseveremalaria.Todeterminewhetherthisbalanceismaintainedbyclassical regulatoryTcells (CD4 + + FOXP3 CD1272/low;Tregs)wecomparedcellularresponsesbetweenGambianchildren(n=124)withseverePlasmodium falciparum malaria or uncomplicated malaria infections. Although no significant differences in Treg numbers or function were observed between the groups, Treg activity during acute disease was inversely correlated with malaria-specific memoryresponsesdetectable28dayslater.Thus,whileTregsmaynotregulateacutemalarialinflammation,theymaylimit memoryresponsestolevelsthatsubsequentlyfacilitateparasiteclearancewithoutcausingimmunopathology.Importantly, we identified a population of FOXP32, CD45RO+ + CD4 T cells which coproduce IL-10 and IFN-c. These cells are more prevalent in children with uncomplicated malaria than in those with severe disease, suggesting that they may be the regulatorsofacutemalarialinflammation. Citation:WaltherM,JeffriesD,FinneyOC,NjieM,EbonyiA,etal.(2009)DistinctRolesforFOXP3+andFOXP32CD4+TCellsinRegulatingCellularImmunityto UncomplicatedandSeverePlasmodiumfalciparumMalaria.PLoSPathog5(4):e1000364.doi:10.1371/journal.ppat.1000364 Editor:JamesW.Kazura,CaseWesternReserveUniversity,UnitedStatesofAmerica Receive