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

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

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

DOI  :  10.1189/jlb.0113018

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 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...

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