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Self-Organized Criticality Theory of Autoimmunity 英文参考文献.doc

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Self-Organized Criticality Theory of Autoimmunity 英文参考文献

Self-OrganizedCriticalityTheoryofAutoimmunity KenTsumiyama1,YumiMiyazaki1,ShunichiShiozawa1,2,3,4* 1DepartmentofBiophysics,KobeUniversityGraduateSchoolofHealthScience,Kobe,Japan,2DepartmentofMedicine,KobeUniversityGraduateSchoolofMedicine, Kobe,Japan,3TheCenterforRheumaticDiseases,KobeUniversityHospital,Kobe,Japan,4GlobalCenterofExcellence(GCOE),Tokyo,Japan Abstract Background: The cause of autoimmunity, which is unknown, is investigated from a different angle, i.e., the defect in immune‘system’,toexplainthecauseofautoimmunity. Methodology/PrincipalFindings:Repeatedimmunizationwithantigencausessystemicautoimmunityinmiceotherwisenot pronetospontaneousautoimmunediseases.OverstimulationofCD4 Tcellsledtothedevelopmentofautoantibody-inducing CD4 T(aiCD4 T)cellwhichhadundergoneTcellreceptor(TCR)revisionandwascapableofinducingautoantibodies.The + + + + + aiCD4 TcellwasinducedbydenovoTCRrevisionbutnotbycross-reaction,andsubsequentlyoverstimulatedCD8 Tcells, drivingthemtobecomeantigen-specificcytotoxicTlymphocytes(CTL).TheseCTLscouldbefurthermaturedbyantigencross- presentation,afterwhichtheycausedautoimmunetissueinjuryakintosystemiclupuserythematosus(SLE). Conclusions/Significance:Systemicautoimmunityappearstobetheinevitableconsequenceofover-stimulatingthehost’s immune‘system’byrepeatedimmunizationwithantigen,tothelevelsthatsurpasssystem’sself-organizedcriticality. Citation: Tsumiyama K, Miyazaki Y, Shiozawa S (2009) Self-Organized Criticality Theory of Autoimmunity. PLoS ONE 4(12): e8382. doi:10.1371/journal. pone.0008382 Editor:DeryaUnutmaz,NewYorkUniversity,UnitedStatesofAmerica ReceivedSeptember11,2009;AcceptedNovember30,2009;PublishedDecember31,2009 Copyright:?2009Tsumiyamaetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding: This work is supported by the Global Center of Excellence (GCOE) Progr