RegulatoryTcellsinembryoimplantationandtheimmuneresponsetopregnancySarahA.Robertson,…,AlisonS.Care,LachlanM.MoldenhauerJClinInvest.2018;128(10):4224-4235.https://doi.org/10.1172/JCI122182.Atimplantation,theembryoexpressespaternallyderivedalloantigensandevokesinflammationthatcanthreatenreproductivesuccess.Toensurearobustplacentaandsustainablepregnancy,anactivestateofmaternalimmunetolerancemediatedbyCD4+regulatoryTcells(Tregs)isessential.Tregsoperatetoinhibiteffectorimmunity,containinflammation,andsupportmaternalvascularadaptations,therebyfacilitatingtrophoblastinvasionandplacentalaccesstothematernalbloodsupply.InsufficientTregnumbersorinadequatefunctionalcompetenceareimplicatedinidiopathicinfertilityandrecurrentmiscarriageaswellaslater-onsetpregnancycomplicationsstemmingfromplacentalinsufficiency,includingpreeclampsiaandfetalgrowthrestriction.InthisReview,wesummarizethemechanismsactingintheconceptionenvironmenttodrivetheTregresponseanddiscussprospectsfortargetingtheTcellcompartmenttoalleviateimmune-basedreproductivedisorders.ReviewFindthelatestversion:http://jci.me/122182/pdfTheJournalofClinicalInvestigationREVIEW4224jci.orgVolume128Number10October2018IntroductionWithindaysofconception,theembryoattachestotheuterinelining,andtrophoblastcellsinvadeintotheuterinedecidua(1).Afinelycontrolleddevelopmentalprogramthenunfolds,withsuccessivewavesoftrophoblastinvasion,proliferation,anddif-ferentiationtoformamatureplacentathatsustainsfetalgrowththroughoutgestation.Thisremarkablefeatoccursinapparentdefianceofthemoth-er’simmuneresponse.Abundantimmunecellsresideinthedecid-uainclosecontactwithinfiltratingtrophoblasts,andpaternallyderivedalloantigensareexpressedinthedevelopingplacentalandfetaltissues.Farfromtheimmuneevasionorsystemicimmunesuppressionhistoricallyinvokedtoexplainmaternal-fetaltoler-ance(2),maternalimmunecellsexhibitprimingtowardfetalallo-antigens(3–5)andactivelyparticipateinmanyaspectsofestab-lishing,sustaining,andterminatingpregnancy(6).Mammalianpregnancycannot...
