Attrition of memory CD8 T cells during sepsis requires LFA‐1

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

关键词: lymphocyte activation;    TCR;    bystander activation;    cytokine;   

DOI  :  10.1189/jlb.4A1215-563RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

CD8Tcelllossanddysfunctionhavebeenimplicatedintheincreasedsusceptibilitytoopportunisticinfectionsduringthelaterimmunosuppressivephaseofsepsis,butCD8Tcellactivationandattritioninearlysepsisremainincompletelyunderstood.WiththeuseofaCLPmodel,weassessedCD8Tcellactivationat5consecutivetimepointsandfoundthatactivationaftersepsisresultsinadistinctphenotype(CD69+CD25intCD62LHI)independentofcognateantigenrecognitionandTCRengagementandlikelythroughbystander‐mediatedcytokineeffects.Additionally,weobservedthatsepsisconcurrentlyresultsinthepreferentialdepletionofasubsetofmemory‐phenotypeCD8Tcellsthatremain“unactivated”(i.e.,failtoup‐regulateactivationmarkers)byapoptosis.UnactivatedCD44HIOT‐Icellsweresparedfromsepsis‐inducedattrition,aswerememory‐phenotypeCD8Tcellsofmicetreatedwithanti‐LFA‐1mAb,1hafterCLP.Perhapsmostimportantly,wedemonstratethatattritionofmemoryphenotypecellsmayhaveapathologicsignificance,aselevatedIL‐6levelswereassociatedwithdecreasednumbersofmemory‐phenotypeCD8Tcellsinsepticmice,andpreservationofthissubsetafteradministrationofanti‐LFA‐1mAbconferredimprovedsurvivalat7d.Takentogether,thesedataidentifypotentiallymodifiableresponsesofmemory‐phenotypeCD8Tcellsinearlysepsisandmaybeparticularlyimportantintheapplicationofimmunomodulatorytherapiesinsepsis...

【 授权许可】

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