Negative Feedback Regulation of T Cells via Interleukin-2 and FOXP3 Reciprocity 英文参考文献.docVIP

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Negative Feedback Regulation of T Cells via Interleukin-2 and FOXP3 Reciprocity 英文参考文献.doc

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Negative Feedback Regulation of T Cells via Interleukin-2 and FOXP3 Reciprocity 英文参考文献

NegativeFeedbackRegulationofTCellsviaInterleukin-2 andFOXP3Reciprocity ZoranPopmihajlov,KendallA.Smith* DivisionofImmunology,DepartmentofMedicine,WeillMedicalCollege,CornellUniversity,NewYork,NewYork,UnitedStatesofAmerica Abstract Asinterleukin-2(IL2)iscentraltotheclonalexpansionofantigen-selectedTcells,weinvestigatedtherelationshipbetween IL2andthenegativeregulatorytranscriptionfactorFOXP3.WefoundIL2toberesponsibleforTcellantigenreceptor(TCR)- activatedFOXP3expressionbybothCD4+andCD8+humanTcells,andasanticipated,FOXP3expressionrestrictedTCR- stimulated IL2 expression. However, no evidence could be found that FOXP3+ cells actively suppress IL2 expression by FOXP3-cells.ThesedataareconsistentwithanIL2/FOXP3-dependentnegativefeedbackloopthatnormallyregulatestheT cellimmuneresponse.ItfollowsthatadefectinthisnegativefeedbackloopasaresultofadeficiencyofeitherIL2orFOXP3 willleadtoahyperproliferativeautoimmunesyndrome,withoutthenecessityofinvokinganactivesuppressivefunctionfor FOXP3+Tcells. Citation:PopmihajlovZ,SmithKA(2008)NegativeFeedbackRegulationofTCellsviaInterleukin-2andFOXP3Reciprocity.PLoSONE3(2):e1581.doi:10.1371/ journal.pone.0001581 Editor:DeryaUnutmaz,NewYorkUniversitySchoolofMedicine,UnitedStatesofAmerica ReceivedNovember20,2007;AcceptedJanuary14,2008;PublishedFebruary13,2008 Copyright:?2008Popmihajlov,Smith.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:NIAID/NIH,BelferFoundation.Neitherfundingsourceparticipatedintheconductofthestudy,inthecollection,analysis,intrpretationofthedata,orin thepreparation,revieworapprovalofthemanuscript. CompetingInterests:Theauthorshavedeclaredthatnocompetinginterestsexist. *E-mail:kasmith@ Introduction Ataboutthistimethescurfymutantmouse[9]wasfoundtobe suffering from a similar lymphoproliferative phenotype [10,11], which was attributed to an over-expression of cy