Decreased frequency of CD73+CD8+ T cells of HIV‐infected patients correlates with immune activation and T cell exhaustion

[摘要] RecentstudiesindicatethatmurineTregshighlyexpresstheENTDP1,aswellasthe5′‐NTandthereby,suppressTefffunctionbyextracellularadenosineproduction.Furthermore,CD73seemstoplayaroleascostimulatorymoleculeforTcelldifferentiation.Inthisstudy,weanalyzedtheexpressionofCD73onperipheralandlymphnodalTeffsandTregsinacohortof95HIVpatientsatdifferentstagesofdisease,includingLTNPandECs.IncontrasttomurineTregs,CD73wasonlyexpressedonasmallminority(∼10%)ofperipheralTregs.Incontrast,weseehighexpressionofCD73onperipheralCD8+Tcells.InHIVinfection,CD73ismarkedlyreducedonallTeffsandTregs,regardlessofthememorysubtype.OnCD8+Tcells,apositivecorrelationbetweenCD73expressionandCD4counts(P=0.0003)wasdetected.CD73expressiononCD8+TcellsnegativelycorrelatedwithHLA‐DR(<0.0001)andPD1(P=0.0457)expression.ThelowerCD73expressiononCD8+TcellswaspartiallyreversibleafterinitiationofART(P=0.0016).Functionally,weobservedthatCD8+CD73+TcellsproducemoreIL‐2uponHIV‐specificandunspecificstimulationthantheirCD73−counterpartsandshowahigherproliferativecapacity.Thesedataindicatethatdown‐regulationofCD73onCD8+TcellscorrelateswithimmuneactivationandleadstofunctionaldeficitsinHIVinfection...

[学科分类] 生理学

[关键词] regulatory T cell;5′‐ectonucleotidase;CD39;elite controller;adenosine