Induction of HIF‐1α and the glycolytic pathway alters apoptotic and differentiation profiles of activated human T cells

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

关键词: activation;    oxygen;    proliferation;    flow cytometry;   

DOI  :  10.1189/jlb.0509304

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ThemajorityofinvitrostudiesinvolvinglymphocytesisperformedinAtmO2,andthePhysO2thatTcellsencounterarevariablebutcommonlymuchlower.PreviousstudiesshowedchangedkineticsanddelayedproliferationofhumanTcellsatPhysO2.Here,weshowthatCD3/CD28‐dependentTcellactivationinducesfastercellcyclingatAtmO2thanatPhysO2(heretakentobe2%).ConcomitantlywithHIF‐1αexpression,weobservedaswitchintheTcellrespiratorypathwaytowardglycolysisatPhysO2.Thus,modulatingavailableglucoselevelsshowedthatatPhysO2,Tcellsrelymoreonglycolysis,associatedwithahigherphosphorylationofAktser473.Althoughnodifferenceinspontaneousapoptosisofrestingcellswasdetected,itwasincreasedsignificantlyatPhysO2afterTcellactivationandwasdifferentwithinthedifferentTcellsubsets.ThismayexplainatleastpartlythedifferentlyalteredproliferationandsubsetdistributionobservedinCD4+andCD8+Tcellsasaresultofdifferencesinnaïveandmemorysubsetdistribution.Together,thesefindingssuggestthatTcellactivationthresholds,subsequentproliferativecapacity,andsusceptibilitytoapoptosis,hithertostudiedinairandthoughttobecrucialformonitoringimmuneresponsiveness,mayrequirere‐assessment...

【 授权许可】

CC BY