CD4+ T Cell-Derived IL-2 Signals during Early Priming Advances Primary CD8+ T Cell Responses 英文参考文献.docVIP

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CD4+ T Cell-Derived IL-2 Signals during Early Priming Advances Primary CD8+ T Cell Responses 英文参考文献.doc

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CD4+TCell-DerivedIL-2SignalsduringEarlyPriming AdvancesPrimaryCD8 TCellResponses + Yo-PingLai1,Chia-ChingLin2,Wan-JungLiao2,Chih-YungTang3,Shu-ChingChen2* 1DepartmentofInternalMedicine,NationalTaiwanUniversityHospital,Taipei,Taiwan,2DepartmentofMedicalResearch,NationalTaiwanUniversityHospital,Taipei, Taiwan,3GraduateInstituteofPhysiology,CollegeofMedicine,NationalTaiwanUniversity,Taipei,Taiwan Abstract Stimulating na?¨ve CD8+ T cells with specific antigens and costimulatory signals is insufficient to induce optimal clonal expansionandeffectorfunctions.Inthisstudy,weshowthattheactivationanddifferentiationofCD8 TcellsrequireIL-2 + + providedbyactivatedCD4 Tcellsattheinitialprimingstagewithin0–2.5hoursafterstimulation.ThiscriticalIL-2signal from CD4 cells is mediated through the IL-2Rbc of CD8 cells, which is independent of IL-2Ra. The activation of IL-2 + + + signalingadvancestherestrictionpointofthecellcycle,andtherebyexpeditestheentryofantigen-stimulatedCD8 T-cell into the S phase. Besides promoting cell proliferation, IL-2 stimulation increases the amount of IFNc and granzyme B + produced by CD8 T cells. Furthermore, IL-2 at priming enhances the ability of P14 effector cells generated by antigen activation to eradicate B16.gp33 tumors in vivo. Therefore, our studies demonstrate that a full CD8 T-cell response is + + elicitedbyacriticaltemporalfunctionofIL-2releasedfromCD4 Tcells,providingmechanisticinsightsintotheregulation ofCD8 Tcellactivationanddifferentiation. + Citation:LaiY-P,LinC-C,LiaoW-J,TangC-Y,ChenS-C(2009)CD4+TCell-DerivedIL-2SignalsduringEarlyPrimingAdvancesPrimaryCD8+TCellResponses.PLoS ONE4(11):e7766.doi:10.1371/journal.pone.0007766 Editor:Jo¨rgHermannFritz,UniversityofToronto,Canada ReceivedMay6,2009;AcceptedSeptember30,2009;PublishedNovember10,2009 Copyright:?2009Laietal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted use,distribution,andreproductioninanymed