Sensitivity of dendritic cells to NK‐mediated lysis depends on the inflammatory environment and is modulated by CD54/CD226‐driven interactions

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: cytotoxicity;    cytokine;    immune modulation;   

DOI  :  10.1189/jlb.3A0615-271RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

PreviousstudieshavesuggestedthatNKcellsmaylimitTcellresponsesbytheirabilitytoeradicatedendriticcells,asdemonstratedbyNKcell‐mediatedkillingofdendriticcellsgeneratedfrommousebonemarrowcellsorhumanmonocyteswithGM‐CSF.Inthepresentstudy,wedemonstratedthatconventionaldendriticcells,generatedinvitrowithFlt3ligandorfromspleens,wereresistanttoNKcell‐mediatedlysis.However,uponstimulationwithGM‐CSF,NKcellscouldmediatelysisofthesedendriticcells.GM‐CSF‐stimulatedFlt3liganddendriticcellsorsplenicdendriticcellsincreasedsurfaceexpressionofcostimulatorymoleculesandknownNKcellligands.Likewise,NKcellscouldtargetdendriticcellsinvivo,whichcouldbeinhibited,inpart,byanti‐GM‐CSFantibodies.TheblockingofCD54orCD226inhibitedNKcell‐mediatedcytotoxicityoftheGM‐CSF‐stimulatedFlt3ligandconventionaldendriticcells.Furthermore,theCD226+NKG2A−subsetofNKcellswasselectivelybetterattargetingGM‐CSF‐stimulatedFlt3ligandconventionaldendriticcells.However,CD155,aknownligandforCD226,couldalsoactasaninhibitorofNKcell‐mediatedlysis,asdendriticcellslackingCD155weremoresensitivetoNKcell‐mediatedlysisthanwild‐typedendriticcells.WehypothesizethatbyonlypermittingasubsetofNKcellstotargetactivateddendriticcellsduringinflammation,thiswouldallowtheimmunesystemtobalancebetweendendriticcellsabletodriveadaptiveimmuneresponsesanddendriticcellstargetedforeliminationbyNKcellstohinder,e.g.,spreadofinfection...

【 授权许可】

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