Upregulation of programmed death-1 on T cells and programmed death ligand-1 on monocytes in septic shock patients 英文参考文献.docVIP

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Upregulation of programmed death-1 on T cells and programmed death ligand-1 on monocytes in septic shock patients 英文参考文献.doc

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Upregulation of programmed death-1 on T cells and programmed death ligand-1 on monocytes in septic shock patients 英文参考文献

Zhangetal.CriticalCare2011,15:R70 /content/15/1/R70 RESEARCH OpenAccess Upregulationofprogrammeddeath-1onTcells andprogrammeddeathligand-1onmonocytes insepticshockpatients YanZhang1?,JinbaoLi2?,JingshengLou2?,YingZhou1,LulongBo2,JialiZhu2,KemingZhu2,XiaojianWan2, ZailongCai1*,XiaomingDeng2* Abstract Introduction:Studiesontheroleofprogrammeddeath-1(PD-1)anditsmainligand(PD-L1)duringexperimental modelsofsepsishaveshownthatthePD-1/PD-L1pathwayplaysapathologicroleinalteringmicrobialclearance, theinnateinflammatoryresponseandacceleratedapoptosisinsepsis.However,theexpressionofPD-1andPD-L1 andtheirroleduringthedevelopmentofimmunesuppressioninsepticpatientshavenotbeenelucidated.The presentstudywasdesignedtodeterminewhethertheexpressionofPD-1andPD-L1isupregulatedinseptic shockpatientsandtoexploretheroleofthispathwayinsepsis-inducedimmunosuppression. Methods:Nineteensepticshockpatientsand22sex-matchedandage-matchedhealthycontrolswere prospectivelyenrolled.ApoptosisinlymphocytesubpopulationsandPD-1/PD-L1expressiononperipheralTcells,B cellsandmonocytesweremeasuredusingflowcytometry.ApoptosisofTcellsinducedbyTNFaorT-cellreceptor ligationinvitroandeffectsofanti-PD-L1antibodyadministrationweremeasuredbyflowcytometry.CD14+ monocytesofsepticshockpatientswerepurifiedandincubatedwitheitherlipopolysaccharide,anti-PD-L1 antibody,isotypeantibody,oracombinationoflipopolysaccharideandanti-PD-L1antibodyorisotypeantibody. SupernatantswereharvestedtoexamineproductionofcytokinesbyELISA. Results:Comparedwithhealthycontrols,septicshockinducedamarkedincreaseinapoptosisasdetectedbythe annexin-Vbindingandactivecaspase-3onCD4+ Tcells,CD8+ TcellsandCD19+ Bcells.ExpressionofPD-1onT cellsandofPD-L1onmonocyteswasdramaticallyupregulatedinsepticshockpatients.PD-1/PD-L1pathway blockadeinvitrowithanti-PD-L1antibodydecreasedapoptosisofTcellsinducedbyTNFaorT-cellreceptor ligation.Meanwhile,thisblockadepotentiatedthelipopolysaccharide-inducedTNFaandIL-6productionand decreasedIL-10productionbymonocytesi