Increased T‐bet is associated with senescence of influenza virus‐specific CD8 T cells in aged humans

[摘要] Agedindividualshaveincreasedmorbidityandmortalityfollowinginfluenzaandotherviralinfections,despitepreviousexposureorvaccination.Mouseandhumanstudiessuggestincreasedsenescenceand/orexhaustionofinfluenzavirus‐specificCD8Tcellswithadvancedage.However,neithertherelationshipbetweensenescenceandexhaustionnortheunderlyingtranscriptionalpathwaysleadingtodecreasedfunctionofinfluenzavirus‐specificcellularimmunityinelderlyhumansarewell‐defined.Here,wedemonstratethatincreasedpercentagesofCD8TcellsfromagedindividualsexpressCD57andKLRG1,alongwithPD‐1andotherinhibitoryreceptors,markersofsenescence,orexhaustion,respectively.ExpressionofT‐boxtranscriptionfactors,T‐betandEomes,werealsoincreasedinCD8TcellsfromagedsubjectsandcorrelatedcloselywithexpressionofCD57andKLRG1.Influenzavirus‐specificCD8TcellsfromagedindividualsexhibiteddecreasedfunctionalitywithcorrespondingincreasesinCD57,KLRG1,andT‐bet,amolecularregulatorofterminaldifferentiation.However,incontrasttototalCD8Tcells,influenzavirus‐specificCD8Tcellshadalteredexpressionofinhibitoryreceptors,includinglowerPD‐1,inagedcomparedwithyoungsubjects.Thus,ourdatasuggestaprominentroleforsenescenceand/orterminaldifferentiationforinfluenzavirus‐specificCD8Tcellsinelderlysubjects...

[学科分类] 生理学

[关键词] CD57;PD‐1;KLRG‐1;Eomes;CD107;exhaustion