Protective CD8 Memory T Cell Responses to Mouse Melanoma Are Generated in the Absence of CD4 T Cell Help 英文参考文献.docVIP

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Protective CD8 Memory T Cell Responses to Mouse Melanoma Are Generated in the Absence of CD4 T Cell Help 英文参考文献.doc

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Protective CD8 Memory T Cell Responses to Mouse Melanoma Are Generated in the Absence of CD4 T Cell Help 英文参考文献

ProtectiveCD8MemoryTCellResponsestoMouse MelanomaAreGeneratedintheAbsenceofCD4TCell Help AnikL.Co?te′.,KatelynT.Byrne.,ShannonM.Steinberg,PeishengZhang,MaryJoTurk* DartmouthMedicalSchoolandtheNorrisCottonCancerCenter,Lebanon,NewHampshire,UnitedStatesofAmerica Abstract Background: We have previously demonstrated that temporary depletion of CD4 T cells in mice with progressive B16 melanoma,followedbysurgicaltumorexcision,inducesprotectivememoryCD8Tcellresponsestomelanoma/melanocyte antigens. We also showed that persistence of these CD8 T cells is supported, in an antigen-dependent fashion, by concurrent autoimmune melanocyte destruction. Herein we explore the requirement of CD4 T cell help in priming and maintainingthisprotectiveCD8Tcellresponsetomelanoma. MethodologyandPrincipalFindings: Toinducemelanoma/melanocyteantigen-specificCD8Tcells,B16tumorbearing miceweredepletedofregulatoryTcells(Treg)byeithertemporary,orlong-termcontinuoustreatmentwithanti-CD4(mAb cloneGK1.5).TotaldepletionofCD4TcellsledtosignificantprimingofIFN-c-producingCD8TcellresponsestoTRP-2and gp100.Surprisingly,treatmentwithanti-CD25(mAbclonePC61),tospecificallydepleteTregcellswhileleavinghelpintact, wasineffectiveatprimingCD8Tcells.Thirtytosixtydaysafterprimarytumorsweresurgicallyexcised,micecompletely lackingCD4Tcellhelpdevelopedautoimmunevitiligo,andmaintainedantigen-specificmemoryCD8Tcellresponsesthat were highly effective at producing cytokines (IFN-c, TNF-a, and IL-2). Mice lacking total CD4 T cell help also mounted protectionagainstre-challengewithB16melanomasixtydaysafterprimarytumorexcision. ConclusionsandSignificance: ThisworkestablishesthatCD4Tcellhelpisdispensableforthegenerationofprotective memoryTcellresponsestomelanoma.OurfindingssupportfurtheruseofCD4Tcelldepletiontherapyforinducinglong- livedimmunitytocancer. Citation:Co?te′AL,ByrneKT,SteinbergSM,ZhangP,TurkMJ(2011)ProtectiveCD8MemoryTCellResponsestoMouseMelanomaAreGeneratedintheAbsence ofCD4TCellHelp.PLoSONE6(10):e26491.doi:10