Regulatory T Cells and Clinical Application PDF
Preview Regulatory T Cells and Clinical Application
Regulatory T Cells and Clinical Application Shuiping Jiang Editor Regulatory T Cells and Clinical Application 123 Editor ShuipingJiang DepartmentofNephrologyandTransplantation Guy’sHospital King’sCollegeLondon LondonSE19RT,UK [email protected] ISBN:978-0-387-77908-9 e-ISBN:978-0-387-77909-6 DOI:10.1007/978-0-387-77909-6 LibraryofCongressControlNumber:2008925544 (cid:2)c 2008SpringerScience+BusinessMedia,LLC Allrightsreserved.Thisworkmaynotbetranslatedorcopiedinwholeorinpartwithoutthewritten permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY10013, USA), except forbrief excerpts inconnection with reviews orscholarly analysis. Usein connection with any form of information storage and retrieval, electronic adaptation, computer software,orbysimilarordissimilarmethodologynowknownorhereafterdevelopedisforbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not theyaresubjecttoproprietaryrights. While the advice and information in this book are believed to be true and accurate at the date of going to press, neither the authors nor the editors nor the publisher can accept any legal responsi- bility for any errors or omissions that may be made. The publisher makes no warranty, express or implied,withrespecttothematerialcontainedherein. Printedonacid-freepaper springer.com Preface AmajorprocessofrediscoveryhastakenplaceinthefieldofCellularImmunology over the past 12 years—subsets of T lymphocytes exist that are specifically ded- icated to regulation or as it should be more appropriately termed suppression of all aspects of immune responses. It is certainly appropriate at this time to recall some of the history that lead to the development of the concept of immune reg- ulation/suppression.Shortly after the term helper T cells was coined to described lymphocytesthat“helped”bothhumoralandcell-mediatedresponses,studiesfrom thelaboratoryofthelateProfessorRichardGershondemonstratedthatundercertain conditions,antigenrecognitionbyTlymphocytesalsoresultedinthedevelopment ofcellsthatareabletosuppressimmuneresponses.Unfortunately,researchinthis fieldrapidlyshiftedfromstudiesofthefunctionofthesuppressorTcellstostudies oftheirsolubleproductsthatwerethoughttobeshedorsecretedT cellreceptors. Anumberofhighlycomplexsuppressorcellpathwaysandcellcircuitsweredevel- opedandwerethesubjectsofmorethan5,000papersduringthisera.In1983–1984, thisfieldcompletelycollapsedasstudiescalledintoquestiontheexistenceoftheI-J regionofthemousemajorhistocompatibilitycomplexthatwas thoughtto encode oneofthe majorchainsofthe suppressorT cellfactors.The cloningof theT cell receptor at that time firmly established that the T cell receptor genes were com- pletelyunrelatedto the genesencodingimmunoglobulinheavychainscallinginto questiontheexistenceofsolubleTcellfactorsthatcontainedimmunoglobulinVH geneproducts.Thenumberofpapersintheliteraturedealingwithsuppressorcells fell from a high of 1,300–1,500/year in 1981 to 150–200/year by the end of the 1980s.At thispointin time, mostimmunologistsfeltit was eveninappropriateto usethetermsuppressorcell! Although a number of workers in the period of 1970–1995continued to focus theirstudiesonTsuppressorcellsratherthansolublefactors,theirworkwaslargely ignored by the immunologic community. The detailed history of their pioneering work will be covered in Chapter 1 by Professor Sakaguchi. Immunologists are somewhatobsessedwithdividingwhatinitiallyappearstobehomogeneouspopu- lationofcells,e.g,CD4+Tlymphocytes,intomultiplesubpopulationswithdistinct functional properties, e.g, Th1 and Th2 cells. Ideally, most immunologists desire that each subpopulation could easily be identified and separated by the expres- sionofacellsurfaceantigenuniquetothatsubpopulation.Althoughimmunologic v vi Preface phenomena that appeared to be mediated by regulatory T cells were described in theliteratureintheearly1990s,whatwasreallymissingfromthisfieldwasacell surface marker that would allow immunologists to define a regulatory/suppressor cell. It was only after Prof. Sakaguchi identified the CD25 antigen in 1995 as a markerforamajorpopulationofTcellsthathadsuppressorfunctionsbothinvitro andinvivothattheresurgenceintheregulatoryTcellareacouldbegin. TheregulatoryTcellsfieldhasgrowndramaticallyoverthepastdecade.Itisnow impossibletoreadajournalthatdoesnotcontainnumerouspaperswhosetitlesdeal withregulatoryTcells.Moreimportantly,itisalsodifficulttosubmitanewresearch grantproposalinanyareaofimmunologicresearchthatdoesnotincludeasection on analysis on the contribution of regulatory T cells to the subject matter under study.Regulatory/SuppressorT cells havecomeof age, again,hopefullythis time tostay.AlthoughitwasinitiallythoughtthatregulatoryTcellsfunctionedprimarily incontrollingautoreactiveimmuneresponsesandseveralchaptersinthisvolumeare devotedtothattopic,thereislittledoubtthattheroleofregulatoryTcellsininfec- tion,cancer,andtransplantationisjustasimportant.RegulatoryTcellsevenappear toplaycriticalrolesincardiovasculardiseaseinthepathogenesisofatherosclerosis. ManyofthechaptersinthisvolumewithdealwiththelineageofregulatoryTcells thataredefinedbyexpressionofCD25andmoreimportantlythetranscriptionfac- torFoxp3.Thesecellswereoriginallybelievedtobegeneratedexclusivelyduring T cell developmentin the thymus, but many recent studies indicate that they can begeneratedextrathymically.CelltypesotherthanCD4+CD25+Foxp3+havealso beenshown to manifestregulatorypropertiesand some of these uniquecell types willbedescribedinChapters23–30. Asinanyrapidlymovingfieldinscience,manyoftheconceptsandtheoriespre- sentedherewillrapidlybemodifiedorevendiscardedasnewstudiesareperformed andnewquestionsareraised.Forexample,therearenowatleastadozenproposed cellularmechanismsforthesuppressiveactivityoftheCD4+CD25+Foxp3+ regu- latory cells. Are all of these suppressive pathways actually used? Which ones are themostimportant?Whichonescanbemanipulatedfortherapeuticpurposes?All of these questionsshould be answered in the next five years. Lastly, an important focusofthisbookisclinicalapplication.Althoughnumerousstudiesinanimalmod- els have strongly suggested that manipulation (augmentation or downregulation) of regulatory T cell function can be used for therapy of autoimmune, neoplastic, or infectious disease, we are now just on the threshold of translating some of the approachesfromanimalsto man. RegulatoryT cells can be best thoughtof today as “teenagers” ready to take on all the challenges of complex immune responses. Intenyears,thefieldwillcertainlybemoremature,andmanipulationofregulatory Tcellfunctionbycellularbiotherapy,antibodiesandsmallmoleculeswillberoutine functionoftheclinicalimmunologist. Bethesda,USA EthanM.Shevach Contents PartI ImmunobiologyofRegulatoryTCells 1 RegulatoryTCellsandtheControlofAuto-Immunity:Fromday3 ThymectomytoFoxP3+RegulatoryTCells ....................... 3 MakotoMiyaraandShimonSakaguchi 2 FoxP3andRegulatoryTCells ................................... 17 KarstenKretschmer,IrinaApostolou,PanosVerginis andHaraldvonBoehmer 3 ThymicandPeripheralGenerationofCD4+Foxp3+ RegulatoryTCells ............................................. 29 PaolaRomagnoli,JulieRibot,JulieTellier,andJoostP.M.vanMeerwijk 4 TheRoleofIL-2intheDevelopmentandPeripheralHomeostasis of Naturally Occurring CD4+CD25+Foxp3+ Regulatory TCells........................................................ 57 AllisonL.BayerandThomasR.Malek 5 IL-2SignalingandCD4+CD25+RegulatoryTCells ............... 77 LouiseM.D’CruzandLudgerKlein 6 TGF-BetaandRegulatoryTCells................................ 91 YisongY.WanandRichardA.Flavell 7 TGF-(cid:2) Regulates Reciprocal Differentiation ofCD4+CD25+Foxp3+ RegulatoryTCellsandIL-17-Producing Th17CellsfromNa¨ıveCD4+CD25– TCells.......................111 WanjunChen 8 MolecularSignallinginTRegulatoryCells .......................135 NatashaR.Locke,NatashaK.CrellinandMeganK.Levings vii viii Contents PartII RegulatoryTCellsinDiseaseandClinicalApplication 9 CD4+Foxp3+ RegulatoryTCellsinImmuneTolerance.............155 CiriacoA.Piccirillo 10 RegulatoryTCellControlofAutoimmuneDiabetesandTheir PotentialTherapeuticApplication................................199 QizhiTangandJeffreyA.Bluestone 11 CD4+CD25+ Regulatory T Cells as Adoptive Cell Therapy for Autoimmune Disease andfortheTreatmentofGraft-Versus-HostDisease................231 SwatiAcharyaandC.GarrisonFathman 12 Natural CD4+CD25+ Regulatory T Cells in Regulation ofAutoimmuneDisease .........................................253 AdamP.KohmandStephenD.Miller 13 MultipleSclerosisandRegulatoryTCells.........................265 JonathonHutton,ClareBaecher-Allan,andDavidA.Hafler 14 CD4+CD25+ Regulatory T Cells and TGF-Beta in Mucosal Inflammation..................................................279 M.FantiniandMarkusF.Neurath 15 Induction of Adaptive CD4+CD25+Foxp3+ Regulatory T Cell ResponseinAutoimmuneDisease ................................293 JianHong,SheriSkinner,andJingwuZhang 16 RegulatoryTCellsinTransplantation............................307 KathrynJWood,AndrewBushell,ManuelaCarvalho-Gaspar, GangFeng,RossFrancis,NickJones,ElaineLong, ShiqiaoLuo,IanLyons,SatishNadig,BirgitSawitzki, GregorWarnecke,BinWei,andJoannaWie˛ckiewicz 17 RegulatoryT-cellsinTherapeuticTransplantationTolerance .......325 HermanWaldmann,ElizabethAdams,PaulFairchild,andStephen Cobbold 18 CD4+CD25+ Regulatory T Cell Therapy for the Induction of ClinicalTransplantationTolerance...............................335 DavidS.Game,RobertI.Lechler,andShuipingJiang 19 RegulatoryTCellsinAllergicDisease ............................355 CatherineHawrylowicz Contents ix 20 RegulatoryTCellsandTumourImmunotherapy ..................379 IlonaKryczekandWeipingZou 21 Regulatory T Cells in Hepatitis andHepatocellularCarcinoma ..................................393 Fu-ShengWangandGeorgeF.Gao 22 CD4+CD25+ RegulatoryTCellsinViralInfections................407 WayneA.Tompkins,MaryB.Tompkins,AngelaM.Mexas, andJonathanE.Fogle 23 IL-10andTGF-(cid:2)-ProducingRegulatoryTCellsinInfection........423 P.J.Dunne,A.G.Rowan,J.M.Fletcher,andKingstonH.G.Mills 24 HumanType1TRegulatoryCells ...............................455 ManuelaBattaglia,SilviaGregori,RosaBacchetta, andMariaGraziaRoncarolo 25 CD8+ T Regulatory Cells in Eye DeriveTolerance...............................................473 JoanStein-StreileinandHiroshiKeino 26 ImmuneSuppressionbyaNovelPopulationofCD8(cid:3)(cid:3)+TCR(cid:3)(cid:2)+ RegulatoryTcells..............................................489 TrevorR.F.SmithandVipinKumar 27 InnateRegulatoryiNKTCells ...................................501 DalamLyandTerryL.Delovitch 28 NaturalKillerTCellsRegulatetheDevelopmentofAsthma ........525 MurielPichavant,RosemarieH.DeKruyff,andDaleT.Umetsu 29 The Development, Activation, Function and Mechanisms ofImmunosuppressiveDoubleNegative(DN)TCells ..............543 MeganS.FordandLiZhang 30 (cid:4)(cid:5)TCellsinImmunoregulation .................................563 LongTang,NingKang,andWeiHe Index .............................................................569 Contributors SwatiAcharya SchoolofMedicine,StanfordUniversity,PaloAlto,CA94305,USA ElizabethAdams SirWilliamDunnSchoolofPathology,UniversityofOxford,SouthParksRoad, OxfordOX13RE,UK IrinaApostolou Harvard Medical School, Dana-Farber Cancer Institute, Harvard University, 44BinneyStreet,Boston,MA02115,USA RosaBacchetta SanRaffaeleTelethonInstituteforGeneTherapy(HSR-TIGET),ViaOlgettina58, Milan20132,Italy ClareBaecher-Allan DivisionofMolecularImmunology,CenterforNeurologicDiseases,Brighamand Women’sHospital,HarvardMedicalSchool,Boston,MA02115,USA ManuelaBattaglia SanRaffaele TelethonInstituteforGeneTherapy(HSR-TIGET);SanRaffaele ScientificInstitute,ImmunologyofDiabetesUnit,ViaOlgettina58,Milan20132, Italy AllisonL.Bayer DepartmentofMicrobiologyandImmunology,DiabetesResearchInstitute,Miller SchoolofMedicine,UniversityofMiami,Miami,FA33136,USA JeffreyA.Bluestone UCSFDiabetesCenter,DepartmentofMedicineandDepartmentofPathology, University of California, 513 Parnassus Avenue, HSW 1118, 513 Parnassus Avenue,SanFrancisco,CA,USA AndrewBushell TransplantationResearchImmunologyGroup,NuffieldDepartmentofSurgery, JohnRadcliffeHospital,UniversityofOxford,OxfordOX39DU,UK xi
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