Technical Advance: Ascorbic acid induces development of double‐positive T cells from human hematopoietic stem cells in the absence of stromal cells

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

关键词: T cell precursor;    DLL4 protein;    adoptive cellular immunotherapy;    transplantation;   

DOI  :  10.1189/jlb.1TA0214-121RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

TheefficacyofdonorHSCTispartlyreducedasaresultofslowpost‐transplantationimmunerecovery.Inparticular,Tcellregenerationisgenerallydelayed,resultinginhighinfection‐relatedmortalityinthefirstyearspost‐transplantation.Adoptivetransferofinvitro‐generatedhumanTcellprogenitorsseemsapromisingapproachtoaccelerateTcellrecoveryinimmunocompromisedpatients.AAmayenhanceTcellproliferationanddifferentiationinacontrolled,feeder‐freeenvironmentcontainingNotchligandsanddefinedgrowthfactors.OurexperimentsshowapivotalroleforAAduringhumaninvitroTcelldevelopment.TheblockingofNOSdiminishedthiseffect,indicatingaroleforthecitrulline/NOcycle.AApromotesthetransitionofproT1toproT2cellsandofpreTtoDPTcells.Furthermore,theadditionofAAtofeedercoculturesresultedindevelopmentofDPandSPTcells,whereaswithoutAA,apreTcell‐stagearrestoccurred.WeconcludethatneitherDLL4‐expressingfeedercellsnorfeedercellconditionedmediaarerequiredforgeneratingDPTcellsfromCBandG‐CSF‐mobilizedHSCsandthatgenerationandproliferationofproTandDPTcellsaregreatlyimprovedbyAA.ThistechnologycouldpotentiallybeusedtogenerateTcellprogenitorsforadoptivetherapy...

【 授权许可】

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