NK cells inhibit humoral immunity by reducing the abundance of CD4+ T follicular helper cells during a chronic virus infection

[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...

[学科分类] 生理学

[关键词] host defense;antibody;immune regulation;lymphocytic choriomeningitis virus;mice