Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
NK cells inhibit humoral immunity by reducing the abundance of CD4+ T follicular helper cells during a chronic virus infection | |
关键词: host defense; antibody; immune regulation; lymphocytic choriomeningitis virus; mice; | |
DOI : 10.1189/jlb.4HI1214-594R | |
学科分类:生理学 | |
来源: Federation of American Societies for Experimental Biology | |
【 摘 要 】
ThereisaneedtounderstandbetterhowtoimproveBcellresponsesandimmunitytopersistingvirusinfections,whichoftencausedebilitatingillnessordeath.Peoplewithchronicvirusinfectionshowevidenceofimprovedviruscontrolwhenthereisastrongneutralizingantibodyresponse,andconversely,Bcelldysfunctionisassociatedwithhigherviralloads.WeshowedpreviouslythatNKcellsinhibitCD4+andCD8+TcellresponsestodisseminatingLCMVinfectionandthatdepletionofNKcellsattenuateschronicinfection.Here,weexaminedtheeffectofNKcelldepletiononBcellresponsestoLCMVinfectioninmice.Whereasmiceinfectedacutelygeneratedapeaklevelofantibodysoonaftertheinfectionwasresolved,miceinfectedchronicallyshowedacontinuedincreaseinantibodylevelsthatexceededthoseafteracuteinfection.WefoundthatearlyNKcelldepletionrapidlyincreasedvirus‐specificantibodylevelstochronicinfection,andthiseffectdependedonCD4+TcellsandwasassociatedwithelevatednumbersofCXCR5+CD4+TFHcells.However,theNKcell‐depletedmicecontrolledtheinfectionandby1mopi,hadlowerTFHcellnumbersandantibodylevelscomparedwithmicewithsustainedinfection.Finally,weshowthatNKcelldepletionimprovedantiviralCD8+TcellresponsesonlywhenBcellsandvirus‐specificantibodywerepresent.OurdataindicatethatNKcellsdiminishimmunitytochronicinfection,inpart,bysuppressingTFHcellandantibodyresponses...
【 授权许可】
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