SH2D2A Modulates T Cell Mediated Protection to a B Cell Derived Tumor in Transgenic Mice 英文参考文献.docVIP

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SH2D2A Modulates T Cell Mediated Protection to a B Cell Derived Tumor in Transgenic Mice 英文参考文献.doc

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SH2D2A Modulates T Cell Mediated Protection to a B Cell Derived Tumor in Transgenic Mice 英文参考文献

SH2D2AModulatesTCellMediatedProtectiontoaBCell DerivedTumorinTransgenicMice ToneBerge1,3*,IngridHeleneB?Gr?nnings?ter1,KristinaBergLorvik2,GregerAbrahamsen1, StineGranum1,VibekeSundvold-Gjerstad1,AlexandreCorthay2,BjarneBogen2,AnneSpurkland1 1Institute of Basic Medical Sciences, Department of Anatomy, University of Oslo, Oslo, Norway, 2Centre for Immune Regulation, Department of Immunology, Oslo UniversityHospitalRikshospitaletandUniversityofOslo,Oslo,Norway,3DepartmentofNeurology,OsloUniversityHospitalUlleva?l, Oslo,Norway Abstract Background:Tcellspecificadapterprotein(TSAd),encodedbytheSH2D2Agene,modulatessignalingdownstreamoftheT cellreceptor(TCR).Young,unchallengedSH2D2A-deficientC57BL/6miceexhibitarelativelynormalimmunephenotype.To address whether SH2D2A regulates physiologic immune responses, SH2D2A-deficient TCR-transgenic BALB/c mice were generated. The transgenic TCR recognizes a myeloma-derived idiotypic (Id) peptide in the context of the major histocompatibility complex (MHC) class II molecule I-Ed, and confers T cell mediated resistance to transplanted multiple myelomadevelopmentinvivo. PrincipalFindings:TheimmunephenotypeofSH2D2A-deficientC57BL/6andBALB/cmicedidnotrevealmajordifferences comparedtothecorrespondingwildtypemice. Whenchallenged withmyelomacells,Id-specific TCR-transgenicBALB/c mice lacking SH2D2A displayed increased resistance towards tumor development. Tumor free TCR-transgenic SH2D2A- deficientmicehadhighernumbersofId-specificsinglepositiveCD4+thymocytescomparedtoTCR-transgenicwild-type mice. Conclusion:OurresultssuggestamodulatoryroleforSH2D2AinTcellmediatedimmunesurveillanceofcancer.However,it remainstobeestablishedwhetheritseffectisT-cellintrinsic.Furtherstudiesarerequiredtodeterminewhethertargeting SH2D2AfunctioninTcellsmaybeapotentialadjuvantincancerimmunotherapy. Citation:BergeT,Gr?nnings?terIHB,LorvikKB,AbrahamsenG,GranumS,etal.(2012)SH2D2AModulatesTCellMediatedProtectiontoaBCellDerivedTumor inTransgenicMice.PLoSONE