ImmunologicalReviews.2019;292:209–224.wileyonlinelibrary.com/journal/imr|2091|INTRODUCTIONCD8+TregswerethefirstsuppressivecellsreportedbutstudieswerethenfocusedonCD4+Tregs.1Overthelasttwodecades,we,alongwithothers,deeplyinvestigatedtheCD8+Tregs.2Todate,significantprogresshavebeenmadeabouttheirphenotype,theirfunctionalmechanisms,andtheirsuppressiveabilitycomparedtoconventionalCD4+Tregs.3Throughthisin‐depthfundamentalre‐search,ithasbeenlearnedmoreabouttheiroriginanddevelopmentandsuchadvanceswillleadtoimprovementintheirgenerationin‐cludingfromstemcells(unpublishedworkdiscussedinthisreview).Celltherapyhasdevelopedinrecentyearsinthefieldoftransplantationandautoimmunediseaseswithpromisingre‐sults.CurrentclinicaltrialsuseTcellsandnon‐Tcells,andamongTregs,FOXP3+andFOXP3−CD4+Tregs(phaseIONE,ALT‐TEN,phaseI/IIaCATS1),butnotCD8+Tregs.WeareatthedawnofthefirstinhumanclinicaltrialusingCD8+Treg‐celltherapyintransplantedpatients(https://www.reshape‐h2020.eu/).ExperiencefrompreviousandcurrentclinicaltrialsusingTcelltherapy,combinedwithourextensiveknowledgeofCD8+Tregs,incrementedbythetechnicalrevolutionofTCellReceptor(TCR)andchimericantigenreceptor(CAR)engineering,insynergywithTregpromotingdrugs,ledustotheEight‐Tregfirstinhumanclinicaltrial.DOI:10.1111/imr.12812INVITEDREVIEWFutureprospectsforCD8+regulatoryTcellsinimmunetoleranceLéaFlippe1,2,3|SéverineBézie1,2,3|IgnacioAnegon1,2,3|CaroleGuillonneau1,2,3ThisarticleispartofaseriesofreviewscoveringToleranceandExhaustioninPeripheralTandBcellsappearinginVolume292ofImmunologicalReviews.1CentredeRechercheenTransplantationetImmunologieUMR1064,INSERM,UniversitédeNantes,Nantes,France2InstitutdeTransplantationUrologieNéphrologie(ITUN),CHUNantes,Nantes,France3LabExIGO“Immunotherapy,Graft,Oncology”,Nantes,FranceCorrespondenceCaroleGuillonneauandIgnacioAnegon,CentredeRechercheenTransplantationetImmunologieINSERM1064‐ITUN,30Bd.JeanMonnet,44093NantesCedex01,France.Email:carole.guillonneau@univ‐nantes.fr(C.G.)andignacio.anegon@un...
