A20 Controls Macrophage to Elicit Potent Cytotoxic CD4+ T Cell Response 英文参考文献.docVIP

A20ControlsMacrophagetoElicitPotentCytotoxicCD4+ TCellResponse LifengWang,BangxingHong,XiaoxiaJiang,LindseyJones,Si-YiChen,XueF.Huang* Norris Comprehensive Cancer Center, Department of Molecular Microbiology Immunology, University ofSouthern California Keck School of Medicine, Los Angeles, California,UnitedStatesofAmerica Abstract Emerging evidence indicates that CD4+ T cells possess cytotoxic potential for tumor eradication and perforin/granzyme- mediated cytotoxicity functions as one of the important mechanisms for CD4 T cell-triggered cell killing. However, the + critical issue is how the cytotoxic CD4+ T cells are developed. During the course of our work that aims at promoting immunostimulation of APCs by inhibition of negative regulators, we found that A20-silenced M drastically induced granzymeBexpressioninCD4 Tcells.Asaconsequence,thegranzyme-highlyexpressingCD4 Tcellsexhibitedastrong + + + cytotoxicactivitythatrestrictedtumordevelopment.WefoundthatA20-silencedM activatedcytotoxicCD4 Tcellsby MHCclass-IIrestrictedmechanismandtheactivationwaslargelydependentonenhancedproductionofIFN-c. Citation:WangL,HongB,JiangX,JonesL,ChenS-Y,etal.(2012)A20ControlsMacrophagetoElicitPotentCytotoxicCD4+TCellResponse.PLoSONE7(11): e48930.doi:10.1371/journal.pone.0048930 Editor:RussellO.Pieper,UniversityofCaliforniaSanFrancisco,UnitedStatesofAmerica ReceivedJuly2,2012;AcceptedOctober2,2012;PublishedNovember7,2012 Copyright: ? 2012 Wang etal. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:TheworkwassupportedbytheNationalInstitutesofHealthresearchgrants(R01CA100841andR21AI087185toXFH,R01CA90427,R0148480and R01AI48711toSYC),andtheresearchgrantfromLeukemiaandLymphomaSociety(toSYC).Thefundershadnoroleinstudydesign,datacollectionandanalysis, decisiontopublish,orpreparationofthemanuscript.