ImmunityReviewHumanTCellDevelopment,Localization,andFunctionthroughoutLifeBrahmaV.Kumar,1ThomasJ.Connors,1,4andDonnaL.Farber1,2,3,*1ColumbiaCenterforTranslationalImmunology,ColumbiaUniversityMedicalCenter,NewYork,NY100322DepartmentofSurgery,ColumbiaUniversityMedicalCenter,NewYork,NY100323DepartmentofMicrobiologyandImmunology,ColumbiaUniversityMedicalCenter,NewYork,NY100324DepartmentofPediatrics,ColumbiaUniversityMedicalCenter,NewYork,NY10032*Correspondence:df2396@cumc.columbia.eduhttps://doi.org/10.1016/j.immuni.2018.01.007Throughoutlife,Tcellscoordinatemultipleaspectsofadaptiveimmunity,includingresponsestopathogens,allergens,andtumors.Inmousemodels,theroleofTcellsisstudiedinthecontextofaspecifictypeofpath-ogen,antigen,ordiseaseconditionoveralimitedtimeframe,whereasinhumans,Tcellscontrolmultiplein-sultssimultaneouslythroughoutthebodyandmaintainimmunehomeostasisoverdecades.Inthisreview,wediscusshowhumanTcellsdevelopandprovideessentialimmuneprotectionatdifferentlifestagesandhighlighttissuelocalizationandsubsetdelineationaskeydeterminantsoftheTcellfunctionalroleinim-muneresponses.Wealsodiscusshowanatomiccompartmentsundergodistinctage-associatedchangesinTcellsubsetcompositionandfunctionoveralifetime.ItisimportanttoconsiderageandtissueinfluencesonhumanTcellswhendevelopingtargetedstrategiestomodulateTcell-mediatedimmunityinvaccinesandimmunotherapies.IntroductionTheestablishmentandmaintenanceofimmuneresponses,ho-meostasis,andmemorydependsonTcells.Tcellsexpressare-ceptorwiththepotentialtorecognizediverseantigensfrompathogens,tumors,andtheenvironmentandalsomaintainimmunologicalmemoryandself-tolerance.Tcellsarealsoimpli-catedasmajordriversofmanyinflammatoryandautoimmunediseases.TheinvivofunctionalroleofTcellsinimmunityandimmunopathologyandtheunderlyingmechanismsinvolvedhavebeenlargelyelucidatedfrommousemodelsandhaveledtothedevelopmentandadvancementofimmune-basedcuresandimmunotherapiesinhumans(Cohen,2014;Rosenberg,2014).However,thepowerandutilityofmousemodelstotesthypothese...
