IL‐21 enhances NK cell functions and survival in healthy and HIV‐infected patients with minimal stimulation of viral replication

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

关键词: LFA‐;    1;    MAPK;    perforin;    STAT‐;    3;   

DOI  :  10.1189/jlb.1009701

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

IL‐21playsanimportantroleinregulatingimmuneresponseandcontrollingchronicviralinfections.Recently,wereporteditsdecreasedserumconcentrationsandtheirimmunologicalconsequencesinHIV‐infectedpersons.Inthisstudy,wehaveinvestigatedhowexogenousIL‐21enhancesNKcellresponsesinthesepersons.WeshowthatthecytokinereceptorsareexpressedequallyonallNKcellsubsetsdefinedbyexpressionofCD16andCD56;thecytokineactivatesSTAT‐3,MAPK,andAkttoenhanceNKcellfunctions;theSTAT‐3activationplaysakeyroleinconstitutiveandIL‐21‐mediatedenhancementofNKcellfunctions;thecytokineincreasesexpressionofantiapoptoticproteinsBcl‐2andBcl‐XLandenhancesviabilityofNKcellsbuthasnoeffectontheirproliferation;thecytokineenhancesHIV‐specificADCC,secretory,andcytotoxicfunctions,aswellasviabilityofNKcellsfromHIV‐infectedpersons;itexertsitsbiologicaleffectsonNKcellswithminimalstimulationofHIV‐1replication;andthecytokine‐activatedNKcellsinhibitviralreplicationincocultured,HIV‐infected,autologousCD4+Tcellsinaperforin‐andLFA‐1‐dependentmanner.ThesedatasuggestthatIL‐21mayserveasavaluabletherapeutictoolforenhancingNKcellresponsesandinhibitingviralreplicationinHIV‐infectedpatients...

【 授权许可】

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