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

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

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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