Cell Density Plays a Critical Role in Ex Vivo Expansion of T Cells for Adoptive Immunotherapy英文文献资料.docVIP

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Cell Density Plays a Critical Role in Ex Vivo Expansion of T Cells for Adoptive Immunotherapy英文文献资料.doc

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Cell Density Plays a Critical Role in Ex Vivo Expansion of T Cells for Adoptive Immunotherapy英文文献资料

HindawiPublishingCorporation JournalofBiomedicineandBiotechnology Volume2010,ArticleID386545,13pages doi:10.1155/2010/386545 ResearchArticle CellDensityPlaysaCriticalRoleinExVivoExpansionof TCellsforAdoptiveImmunotherapy AgnesShuk-YeeLo, EricaM.Gomes, QiangzhongMa,1,2YawenWang,2 2 1 andRichardP.Junghans 1,2 1 BiotherapeuticsDevelopmentLaboratory,RogerWilliamsMedicalCenter,BostonUniversitySchoolofMedicine, Providence,RI02908,USA 2 BethIsraelDeaconessMedicalCenter,HarvardMedicalSchool,Boston,MA02115,USA CorrespondenceshouldbeaddressedtoQiangzhongMa,qma@ Received24December2009;Revised5April2010;Accepted6May2010 AcademicEditor:ZhengguoXiao Copyright?2010QiangzhongMaetal. This is an open access article distributed under the Creative Commons Attribution License,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperly cited. ThesuccessfulexvivoexpansionofalargenumbersofTcellsisaprerequisiteforadoptiveimmunotherapy.Inthisstudy,we foundthatcelldensityhadimportante?ectsontheprocessofexpansionofTcellsinvitro.RestingTcellswereactivatedto expandathighcelldensitybutfailedtobeactivatedatlowcelldensity.ActivatedTcells(ATCs)expandedrapidlyathighcell densitybutunderwentapoptosisatlowcelldensity.Ourstudiesindicatedthatlow-cell-densityrelatedATCdeathismediated byoxidativestress.AntioxidantsN-acetylcysteine,catalase,andalbuminsuppressedelevatedreactiveoxygenspecies(ROS)levels inlow-densityculturesandprotectedATCsfromapoptosis.TheviabilityofATCsatlowdensitywaspreservedbyconditioned medium from high-density cultures of ATCs in which the autocrine survival factor was identi?ed as catalase. We also found thatcostimulatorysignalCD28increasesTcellactivationatlowercelldensity,paralleledbyanincreaseincatalasesecretion. Our?ndingshighlighttheimportanceofcelldensityinTcellactivation,proliferation,survivalandapoptosisandsupportthe importanceofmaintainingTcellsathighdensityfortheirsuccessfulexpansioninvitro. 1.In