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Review

Avoiding Immunological Rejection in Regenerative Medicine

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Pages 287-304 | Published online: 01 May 2015

References

  • Okita K , NagataN, YamanakaS. Immunogenicity of induced pluripotent stem cells. Circ. Res.109 (7), 720–721 (2011).
  • Kaneko S , YamanakaS. To be immunogenic, or not to be: that's the iPSC question. Cell Stem Cell12 (4), 385–386 (2013).
  • Fu X . The immunogenicity of cells derived from induced pluripotent stem cells. Cell Mol. Immunol.11 (1), 14–16 (2014).
  • Araki R , UdaM, HokiYet al. Negligible immunogenicity of terminally differentiated cells derived from induced pluripotent or embryonic stem cells. Nature494 (7435), 100–104 (2013).
  • Guha P , MorganJW, MostoslavskyG, RodriguesNP, BoydAS. Lack of immune response to differentiated cells derived from syngeneic induced pluripotent stem cells. Cell Stem Cell12 (4), 407–412 (2013).
  • Morizane A , DoiD, KikuchiTet al. Direct comparison of autologous and allogeneic transplantation of iPSC-derived neural cells in the brain of a nonhuman primate. Stem Cell Rep.1 (4), 283–292 (2013).
  • Sachamitr P , HackettS, FairchildPJ. Induced pluripotent stem cells: challenges and opportunities for cancer immunotherapy. Front. Immunol.5, 176 (2014).
  • Scheiner ZS , TalibS, FeigalEG. The potential for immunogenicity of autologous induced pluripotent stem cell-derived therapies. J. Biol. Chem.289 (8), 4571–4577 (2014).
  • Tang C , WeissmanIL, DrukkerM. Immunogenicity of in vitro maintained and matured populations: potential barriers to engraftment of human pluripotent stem cell derivatives. Methods Mol. Biol.1029, 17–31 (2013).
  • Kim K , DoiA, WenBet al. Epigenetic memory in induced pluripotent stem cells. Nature467 (7313), 285–290 (2010).
  • Marchetto MC , YeoGW, KainohanaO, MarsalaM, GageFH, MuotriAR. Transcriptional signature and memory retention of human-induced pluripotent stem cells. PLoS ONE4 (9), e7076 (2009).
  • Stelzer Y , YanukaO, BenvenistyN. Global analysis of parental imprinting in human parthenogenetic induced pluripotent stem cells. Nat. Struct. Mol. Biol.18 (6), 735–741 (2011).
  • Zimmermann A , Preynat-SeauveO, TiercyJM, KrauseKH, VillardJ. Haplotype-based banking of human pluripotent stem cells for transplantation: potential and limitations. Stem Cells Dev.21 (13), 2364–2373 (2012).
  • Bradley JA , BoltonEM, PedersenRA. Stem cell medicine encounters the immune system. Nat. Rev. Immunol.2 (11), 859–871 (2002).
  • Drukker M , KatzG, UrbachAet al. Characterization of the expression of MHC proteins in human embryonic stem cells. Proc. Natl Acad. Sci. USA99 (15), 9864–9869 (2002).
  • Drukker M , KatchmanH, KatzGet al. Human embryonic stem cells and their differentiated derivatives are less susceptible to immune rejection than adult cells. Stem Cells24 (2), 221–229 (2006).
  • Taylor CJ , BoltonEM, PocockS, SharplesLD, PedersenRA, BradleyJA. Banking on human embryonic stem cells: estimating the number of donor cell lines needed for HLA matching. Lancet366 (9502), 2019–2025 (2005).
  • Molne J , BjorquistP, AnderssonKet al. Blood group ABO antigen expression in human embryonic stem cells and in differentiated hepatocyte- and cardiomyocyte-like cells. Transplantation86 (10), 1407–1413 (2008).
  • Taylor CJ , PeacockS, ChaudhryAN, BradleyJA, BoltonEM. Generating an iPSC bank for HLA-matched tissue transplantation based on known donor and recipient HLA types. Cell Stem Cell11 (2), 147–152 (2012).
  • Taylor CJ , BoltonEM, BradleyJA. Immunological considerations for embryonic and induced pluripotent stem cell banking. Philos. Trans. R Soc. Lond. B Biol. Sci.366 (1575), 2312–2322 (2011).
  • Sanchez Alvarado A , YamanakaS. Rethinking differentiation: stem cells, regeneration, and plasticity. Cell157 (1), 110–119 (2014).
  • Nakatsuji N , NakajimaF, TokunagaK. HLA-haplotype banking and iPS cells. Nat. Biotechnol.26 (7), 739–740 (2008).
  • Gourraud PA , GilsonL, GirardM, PeschanskiM. The role of human leukocyte antigen matching in the development of multiethnic “haplobank” of induced pluripotent stem cell lines. Stem Cells30 (2), 180–186 (2012).
  • Turner M , LeslieS, MartinNGet al. Toward the development of a global induced pluripotent stem cell library. Cell Stem Cell13 (4), 382–384 (2013).
  • Hunt JS , PetroffMG, McIntireRH, OberC. HLA-G and immune tolerance in pregnancy. FASEB J.19 (7), 681–693 (2005).
  • Munn DH , ZhouM, AttwoodJTet al. Prevention of allogeneic fetal rejection by tryptophan catabolism. Science281 (5380), 1191–1193 (1998).
  • Aluvihare VR , KallikourdisM, BetzAG. Regulatory T cells mediate maternal tolerance to the fetus. Nat. Immunol.5 (3), 266–271 (2004).
  • Trowsdale J , BetzAG. Mother's little helpers: mechanisms of maternal-fetal tolerance. Nat. Immunol.7 (3), 241–246 (2006).
  • Taylor AW , AlardP, YeeDG, StreileinJW. Aqueous humor induces transforming growth factor-beta (TGF-beta)-producing regulatory T-cells. Curr. Eye Res.16 (9), 900–908 (1997).
  • Sharland A , ShastryS, WangCet al. Kinetics of intragraft cytokine expression, cellular infiltration, and cell death in rejection of renal allografts compared with acceptance of liver allografts in a rat model: early activation and apoptosis is associated with liver graft acceptance. Transplantation65 (10), 1370–1377 (1998).
  • Suarez-Alvarez B , RodriguezRM, CalvaneseVet al. Epigenetic mechanisms regulate MHC and antigen processing molecules in human embryonic and induced pluripotent stem cells. PLoS ONE5 (4), e10192 (2010).
  • Land WG . Emerging role of innate immunity in organ transplantation: part II: potential of damage-associated molecular patterns to generate immunostimulatory dendritic cells. Transplant. Rev. (Orlando)26 (2), 73–87 (2012).
  • Land WG . Emerging role of innate immunity in organ transplantation: part I: evolution of innate immunity and oxidative allograft injury. Transplant. Rev. (Orlando)26 (2), 60–72 (2012).
  • Land WG . Emerging role of innate immunity in organ transplantation: part III: the quest for transplant tolerance via prevention of oxidative allograft injury and its consequences. Transplant. Rev. (Orlando)26 (2), 88–102 (2012).
  • Peterson KM , AlyA, LermanA, LermanLO, Rodriguez-PorcelM. Improved survival of mesenchymal stromal cell after hypoxia preconditioning: role of oxidative stress. Life Sci.88 (1–2), 65–73 (2011).
  • Zhu W , ChenJ, CongX, HuS, ChenX. Hypoxia and serum deprivation-induced apoptosis in mesenchymal stem cells. Stem Cells24 (2), 416–425 (2006).
  • Sacks SH , ZhouW. The role of complement in the early immune response to transplantation. Nat. Rev. Immunol.12 (6), 431–442 (2012).
  • Kofidis T , deBruinJL, TanakaMet al. They are not stealthy in the heart: embryonic stem cells trigger cell infiltration, humoral and T-lymphocyte-based host immune response. Eur. J. Cardiothorac. Surg.28 (3), 461–466 (2005).
  • Swijnenburg RJ , TanakaM, VogelHet al. Embryonic stem cell immunogenicity increases upon differentiation after transplantation into ischemic myocardium. Circulation112 (9 Suppl.), I166–172 (2005).
  • Nussbaum J , MinamiE, LaflammeMAet al. Transplantation of undifferentiated murine embryonic stem cells in the heart: teratoma formation and immune response. FASEB J.21 (7), 1345–1357 (2007).
  • Swijnenburg RJ , SchrepferS, CaoFet al. In vivo imaging of embryonic stem cells reveals patterns of survival and immune rejection following transplantation. Stem Cells Dev.17 (6), 1023–1029 (2008).
  • Wu DC , BoydAS, WoodKJ. Embryonic stem cells and their differentiated derivatives have a fragile immune privilege but still represent novel targets of immune attack. Stem Cells26 (8), 1939–1950 (2008).
  • Robertson NJ , BrookFA, GardnerRL, CobboldSP, WaldmannH, FairchildPJ. Embryonic stem cell-derived tissues are immunogenic but their inherent immune privilege promotes the induction of tolerance. Proc. Natl Acad. Sci. USA104 (52), 20920–20925 (2007).
  • Frenzel LP , AbdullahZ, KriegeskorteAKet al. Role of natural-killer group 2 member D ligands and intercellular adhesion molecule 1 in natural killer cell-mediated lysis of murine embryonic stem cells and embryonic stem cell-derived cardiomyocytes. Stem Cells27 (2), 307–316 (2009).
  • Dressel R , NolteJ, ElsnerLet al. Pluripotent stem cells are highly susceptible targets for syngeneic, allogeneic, and xenogeneic natural killer cells. FASEB J.24 (7), 2164–2177 (2010).
  • Preynat-Seauve O , de RhamC, TirefortD, Ferrari-LacrazS, KrauseKH, VillardJ. Neural progenitors derived from human embryonic stem cells are targeted by allogeneic T and natural killer cells. J. Cell Mol. Med.13 (9B), 3556–3569 (2009).
  • Ma M , DingS, LundqvistAet al. Major histocompatibility complex-I expression on embryonic stem cell-derived vascular progenitor cells is critical for syngeneic transplant survival. Stem Cells28 (9), 1465–1475 (2010).
  • Lindahl KF , WilsonDB. Histocompatibility antigen-activated cytotoxic T lymphocytes. II. Estimates of the frequency and specificity of precursors. J. Exp. Med.145 (3), 508–522 (1977).
  • Lindahl KF , WilsonDB. Histocompatibility antigen-activated cytotoxic T lymphocytes. I. Estimates of the absolute frequency of killer cells generated in vitro. J. Exp. Med.145 (3), 500–507 (1977).
  • Matzinger P , BevanMJ. Hypothesis: why do so many lymphocytes respond to major histocompatibility antigens?Cell Immunol.29 (1), 1–5 (1977).
  • Skinner MA , MarbrookJ. An estimation of the frequency of precursor cells which generate cytotoxic lymphocytes. J. Exp. Med.143 (6), 1562–1567 (1976).
  • Afzali B , LombardiG, LechlerRI. Pathways of major histocompatibility complex allorecognition. Curr. Opin. Organ Transplant.13 (4), 438–444 (2008).
  • Bedford P , GarnerK, KnightSC. MHC class II molecules transferred between allogeneic dendritic cells stimulate primary mixed leukocyte reactions. Int. Immunol.11 (11), 1739–1744 (1999).
  • Curry AJ , PettigrewGJ, NegusMCet al. Dendritic cells internalise and represent conformationally intact soluble MHC class I alloantigen for generation of alloantibody. Eur. J. Immunol.37 (3), 696–705 (2007).
  • Sivaganesh S , HarperSJ, ConlonTMet al. Copresentation of intact and processed MHC alloantigen by recipient dendritic cells enables delivery of linked help to alloreactive CD8 T cells by indirect-pathway CD4 T cells. J. Immunol.190 (11), 5829–5838 (2013).
  • Taylor AL , NegusSL, NegusM, BoltonEM, BradleyJA, PettigrewGJ. Pathways of helper CD4 T cell allorecognition in generating alloantibody and CD8 T cell alloimmunity. Transplantation83 (7), 931–937 (2007).
  • Wood KJ , GotoR. Mechanisms of rejection: current perspectives. Transplantation93 (1), 1–10 (2012).
  • Okita K , MatsumuraY, SatoYet al. A more efficient method to generate integration-free human iPS cells. Nat. Methods8 (5), 409–412 (2011).
  • Day E , KearnsPK, TaylorCJ, BradleyJA. Transplantation between monozygotic twins: how identical are they?Transplantation98 (5), 485–489 (2014).
  • Rostaing L , SalibaF, CalmusY, DharancyS, BoillotO. Review article: use of induction therapy in liver transplantation. Transplant. Rev. (Orlando)26 (4), 246–260 (2012).
  • Morgan RD , O'CallaghanJM, KnightSR, MorrisPJ. Alemtuzumab induction therapy in kidney transplantation: a systematic review and meta-analysis. Transplantation93 (12), 1179–1188 (2012).
  • Rush D . The impact of calcineurin inhibitors on graft survival. Transplant. Rev. (Orlando)27 (3), 93–95 (2013).
  • Salvadori M , BertoniE. Is it time to give up with calcineurin inhibitors in kidney transplantation?World J. Transplant.3 (2), 7–25 (2013).
  • Russ GR . Optimising the use of mTOR inhibitors in renal transplantation. Transplant. Res.2 (Suppl. 1), S4 (2013).
  • Gurk-Turner C , ManitpisitkulW, CooperM. A comprehensive review of everolimus clinical reports: a new mammalian target of rapamycin inhibitor. Transplantation94 (7), 659–668 (2012).
  • Davies NM , GrinyoJ, HeadingR, MaesB, Meier-KriescheHU, OellerichM. Gastrointestinal side effects of mycophenolic acid in renal transplant patients: a reappraisal. Nephrol. Dial. Transplant.22 (9), 2440–2448 (2007).
  • Jordan SC , KahwajiJ, ToyodaM, VoA. B-cell immunotherapeutics: emerging roles in solid organ transplantation. Curr. Opin. Organ Transplant.16 (4), 416–424 (2011).
  • Wojciechowski D , VincentiF. Belatacept in kidney transplantation. Curr. Opin. Organ Transplant.17 (6), 640–647 (2012).
  • Kotton CN . CMV: prevention, diagnosis and therapy. Am. J. Transplant.13 (Suppl. 3), 24–40 ; quiz 40 (2013).
  • Shoham S , MarrKA. Invasive fungal infections in solid organ transplant recipients. Future Microbiol.7 (5), 639–655 (2012).
  • Euvrard S , KanitakisJ, ClaudyA. Skin cancers after organ transplantation. N. Engl. J. Med.348 (17), 1681–1691 (2003).
  • Taylor AL , MarcusR, BradleyJA. Post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation. Crit. Rev. Oncol. Hematol.56 (1), 155–167 (2005).
  • Green M , MichaelsMG. Epstein-Barr virus infection and posttransplant lymphoproliferative disorder. Am. J. Transplant.13 (Suppl. 3), 41–54 ; quiz 54 (2013).
  • Euvrard S , MorelonE, RostaingLet al. Sirolimus and secondary skin-cancer prevention in kidney transplantation. N. Engl. J. Med.367 (4), 329–339 (2012).
  • Pearl JI , LeeAS, Leveson-GowerDBet al. Short-term immunosuppression promotes engraftment of embryonic and induced pluripotent stem cells. Cell Stem Cell8 (3), 309–317 (2011).
  • Swijnenburg RJ , SchrepferS, GovaertJAet al. Immunosuppressive therapy mitigates immunological rejection of human embryonic stem cell xenografts. Proc. Natl Acad. Sci. USA105 (35), 12991–12996 (2008).
  • Grinnemo KH , GeneadR, Kumagai-BraeschMet al. Costimulation blockade induces tolerance to HESC transplanted to the testis and induces regulatory T-cells to HESC transplanted into the heart. Stem Cells26 (7), 1850–1857 (2008).
  • Ludwig B , ReichelA, SteffenAet al. Transplantation of human islets without immunosuppression. Proc. Natl Acad. Sci. USA110 (47), 19054–19058 (2013).
  • McCall M , ShapiroAM. Update on islet transplantation. Cold Spring Harb. Perspect. Med.2 (7), a007823 (2012).
  • Posselt AM , SzotGL, FrassettoLAet al. Islet transplantation in type 1 diabetic patients using calcineurin inhibitor-free immunosuppressive protocols based on T-cell adhesion or costimulation blockade. Transplantation90 (12), 1595–1601 (2010).
  • Nienhuis AW . Development of gene therapy for blood disorders: an update. Blood122 (9), 1556–1564 (2013).
  • Mitani K . Gene targeting in human-induced pluripotent stem cells with adenoviral vectors. Methods Mol. Biol.1114, 163–167 (2014).
  • Gonzalez S , CastanottoD, LiHet al. Amplification of RNAi‐‐targeting HLA mRNAs. Mol. Ther.11 (5), 811–818 (2005).
  • Zhao J , BoltonEM, OrmistonML, BradleyJA, MorrellNW, LeverAM. Late outgrowth endothelial progenitor cells engineered for improved survival and maintenance of function in transplant-related injury. Transpl. Int.25 (2), 229–241 (2012).
  • Zhao J , PettigrewGJ, BoltonEMet al. Lentivirus-mediated gene transfer of viral interleukin-10 delays but does not prevent cardiac allograft rejection. Gene Ther.12 (20), 1509–1516 (2005).
  • Raya A , Rodriguez-PizaI, GuenecheaGet al. Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells. Nature460 (7251), 53–59 (2009).
  • Yusa K , RashidST, Strick-MarchandHet al. Targeted gene correction of alpha1-antitrypsin deficiency in induced pluripotent stem cells. Nature478 (7369), 391–394 (2011).
  • Matrai J , ChuahMK, VandenDriesscheT. Recent advances in lentiviral vector development and applications. Mol. Ther.18 (3), 477–490 (2010).
  • Gaj T , GersbachCA, BarbasCF, 3rd. ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol.31 (7), 397–405 (2013).
  • Figueiredo C , WedekindD, MullerTet al. MHC universal cells survive in an allogeneic environment after incompatible transplantation. Biomed. Res. Int.2013, 796046 (2013).
  • Torikai H , ReikA, SoldnerFet al. Toward eliminating HLA class I expression to generate universal cells from allogeneic donors. Blood122 (8), 1341–1349 (2013).
  • Qian S , FuF, LiYet al. Impact of donor MHC class I or class II antigen deficiency on first- and second-set rejection of mouse heart or liver allografts. Immunology88 (1), 124–129 (1996).
  • Hacke K , FalahatiR, Flebbe-RehwaldtL, KasaharaN, GaenslerKM. Suppression of HLA expression by lentivirus-mediated gene transfer of siRNA cassettes and in vivo chemoselection to enhance hematopoietic stem cell transplantation. Immunol. Res.44 (1–3), 112–126 (2009).
  • Figueiredo C , SeltsamA, BlasczykR. Class-, gene-, and group-specific HLA silencing by lentiviral shRNA delivery. J. Mol. Med. (Berl).84 (5), 425–437 (2006).
  • Beilke JN , BenjaminJ, LanierLL. The requirement for NKG2D in NK cell-mediated rejection of parental bone marrow grafts is determined by MHC class I expressed by the graft recipient. Blood116 (24), 5208–5216 (2010).
  • Rolstad B . The early days of NK cells: an example of how a phenomenon led to detection of a novel immune receptor system – lessons from a rat model. Front. Immunol.5, 283 (2014).
  • Belanger S , TuMM, RahimMMet al. Impaired natural killer cell self-education and ‘missing-self’ responses in Ly49-deficient mice. Blood120 (3), 592–602 (2012).
  • Matheux F , VillardJ. Cellular and gene therapy for major histocompatibility complex class II deficiency. News Physiol. Sci.19, 154–158 (2004).
  • Jaimes Y , SeltsamA, Eiz-VesperB, BlasczykR, FigueiredoC. Regulation of HLA class II expression prevents allogeneic T-cell responses. Tissue Antigens77 (1), 36–44 (2011).
  • Ke B , BuelowR, ShenXDet al. Heme oxygenase 1 gene transfer prevents CD95/Fas ligand-mediated apoptosis and improves liver allograft survival via carbon monoxide signaling pathway. Hum. Gene Ther.13 (10), 1189–1199 (2002).
  • Li J , MeinhardtA, RoehrichMEet al. Indoleamine 2,3-dioxygenase gene transfer prolongs cardiac allograft survival. Am. J. Physiol. Heart Circ. Physiol.293 (6), H3415–H3423 (2007).
  • Olthoff KM , JudgeTA, GelmanAEet al. Adenovirus-mediated gene transfer into cold-preserved liver allografts: survival pattern and unresponsiveness following transduction with CTLA4Ig. Nat. Med.4 (2), 194–200 (1998).
  • Kim YH , LimDG, WeeYMet al. Viral IL-10 gene transfer prolongs rat islet allograft survival. Cell Transplant.17 (6), 609–618 (2008).
  • Tomasoni S , AzzolliniN, CasiraghiF, CapogrossiMC, RemuzziG, BenigniA. CTLA4Ig gene transfer prolongs survival and induces donor-specific tolerance in a rat renal allograft. J. Am. Soc. Nephrol.11 (4), 747–752 (2000).
  • Dudler J , LiJ, PagnottaM, PascualM, von SegesserLK, VassalliG. Gene transfer of programmed death ligand-1.Ig prolongs cardiac allograft survival. Transplantation82 (12), 1733–1737 (2006).
  • Friedenstein AJ , GorskajaJF, KulaginaNN. Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp. Hematol.4 (5), 267–274 (1976).
  • Pittenger MF , MackayAM, BeckSCet al. Multilineage potential of adult human mesenchymal stem cells. Science284 (5411), 143–147 (1999).
  • Fraser JK , WulurI, AlfonsoZ, HedrickMH. Fat tissue: an underappreciated source of stem cells for biotechnology. Trends Biotechnol.24 (4), 150–154 (2006).
  • Schallmoser K , RohdeE, ReinischAet al. Rapid large-scale expansion of functional mesenchymal stem cells from unmanipulated bone marrow without animal serum. Tissue Eng. Part C Methods.14 (3), 185–196 (2008).
  • Kuhbier JW , WeyandB, RadtkeC, VogtPM, KasperC, ReimersK. Isolation, characterization, differentiation, and application of adipose-derived stem cells. Adv. Biochem. Eng. Biotechnol.123, 55–105 (2010).
  • Ankrum J , KarpJM. Mesenchymal stem cell therapy: two steps forward, one step back. Trends Mol. Med.16 (5), 203–209 (2010).
  • Lalu MM , McIntyreL, PuglieseCet al. Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials. PLoS ONE7 (10), e47559 (2012).
  • Lalu MM , McIntyreLL, StewartDJ. Mesenchymal stromal cells: cautious optimism for their potential role in the treatment of acute lung injury. Crit. Care Med.40 (4), 1373–1375 (2012).
  • Krampera M , GlennieS, DysonJet al. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood101 (9), 3722–3729 (2003).
  • Glennie S , SoeiroI, DysonPJ, LamEW, DazziF. Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood105 (7), 2821–2827 (2005).
  • Le Blanc K , TammikL, SundbergB, HaynesworthSE, RingdenO. Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand. J. Immunol.57 (1), 11–20 (2003).
  • Ryan JM , BarryFP, MurphyJM, MahonBP. Mesenchymal stem cells avoid allogeneic rejection. J. Inflamm. (Lond).2, 8 (2005).
  • Le Blanc K , FrassoniF, BallLet al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet371 (9624), 1579–1586 (2008).
  • Ringden O , UzunelM, RasmussonIet al. Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation81 (10), 1390–1397 (2006).
  • Ding Y , XuD, FengG, BushellA, MuschelRJ, WoodKJ. Mesenchymal stem cells prevent the rejection of fully allogenic islet grafts by the immunosuppressive activity of matrix metalloproteinase-2 and -9. Diabetes58 (8), 1797–1806 (2009).
  • Casiraghi F , AzzolliniN, CassisPet al. Pretransplant infusion of mesenchymal stem cells prolongs the survival of a semiallogeneic heart transplant through the generation of regulatory T cells. J. Immunol.181 (6), 3933–3946 (2008).
  • Inoue S , PoppFC, KoehlGEet al. Immunomodulatory effects of mesenchymal stem cells in a rat organ transplant model. Transplantation81 (11), 1589–1595 (2006).
  • Peng Y , KeM, XuLet al. Donor-derived mesenchymal stem cells combined with low-dose tacrolimus prevent acute rejection after renal transplantation: a clinical pilot study. Transplantation95 (1), 161–168 (2013).
  • Ramasamy R , TongCK, SeowHF, VidyadaranS, DazziF. The immunosuppressive effects of human bone marrow-derived mesenchymal stem cells target T cell proliferation but not its effector function. Cell Immunol.251 (2), 131–136 (2008).
  • Di Nicola M , Carlo-StellaC, MagniMet al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood99 (10), 3838–3843 (2002).
  • Corcione A , BenvenutoF, FerrettiEet al. Human mesenchymal stem cells modulate B-cell functions. Blood107 (1), 367–372 (2006).
  • Beyth S , BorovskyZ, MevorachDet al. Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood105 (5), 2214–2219 (2005).
  • Augello A , TassoR, NegriniSMet al. Bone marrow mesenchymal progenitor cells inhibit lymphocyte proliferation by activation of the programmed death 1 pathway. Eur. J. Immunol.35 (5), 1482–1490 (2005).
  • Krampera M , CosmiL, AngeliRet al. Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells24 (2), 386–398 (2006).
  • Madec AM , MalloneR, AfonsoGet al. Mesenchymal stem cells protect NOD mice from diabetes by inducing regulatory T cells. Diabetologia52 (7), 1391–1399 (2009).
  • Sato K , OzakiK, OhIet al. Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood109 (1), 228–234 (2007).
  • Ramasamy R , FazekasovaH, LamEW, SoeiroI, LombardiG, DazziF. Mesenchymal stem cells inhibit dendritic cell differentiation and function by preventing entry into the cell cycle. Transplantation83 (1), 71–76 (2007).
  • Probst HC , McCoyK, OkazakiT, HonjoT, van den BroekM. Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4. Nat. Immunol.6 (3), 280–286 (2005).
  • Reis e Sousa C . Dendritic cells in a mature age. Nat. Rev. Immunol.6 (6), 476–483 (2006).
  • Albert ML , JegathesanM, DarnellRB. Dendritic cell maturation is required for the cross-tolerization of CD8+ T cells. Nat. Immunol.2 (11), 1010–1017 (2001).
  • Penna G , AdoriniL. 1 Alpha,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J. Immunol.164 (5), 2405–2411 (2000).
  • Hackstein H , MorelliAE, LarreginaATet al. Aspirin inhibits in vitro maturation and in vivo immunostimulatory function of murine myeloid dendritic cells. J. Immunol.166 (12), 7053–7062 (2001).
  • Woltman AM , de FijterJW, KamerlingSW, PaulLC, DahaMR, van KootenC. The effect of calcineurin inhibitors and corticosteroids on the differentiation of human dendritic cells. Eur. J. Immunol.30 (7), 1807–1812 (2000).
  • Piemonti L , MontiP, AllavenaPet al. Glucocorticoids affect human dendritic cell differentiation and maturation. J. Immunol.162 (11), 6473–6481 (1999).
  • Vieira PL , KalinskiP, WierengaEA, KapsenbergML, de JongEC. Glucocorticoids inhibit bioactive IL-12p70 production by in vitro-generated human dendritic cells without affecting their T cell stimulatory potential. J. Immunol.161 (10), 5245–5251 (1998).
  • Ramirez F , FowellDJ, PuklavecM, SimmondsS, MasonD. Glucocorticoids promote a TH2 cytokine response by CD4+ T cells in vitro. J. Immunol.156 (7), 2406–2412 (1996).
  • Chen T , GuoJ, YangMet al. Cyclosporin A impairs dendritic cell migration by regulating chemokine receptor expression and inhibiting cyclooxygenase-2 expression. Blood103 (2), 413–421 (2004).
  • Hoves S , KrauseSW, HerfarthHet al. Elimination of activated but not resting primary human CD4+ and CD8+ T cells by Fas ligand (FasL/CD95L)-expressing Killer-dendritic cells. Immunobiology208 (5), 463–475 (2004).
  • Feili-Hariri M , FalknerDH, GambottoAet al. Dendritic cells transduced to express interleukin-4 prevent diabetes in nonobese diabetic mice with advanced insulitis. Hum. Gene Ther.14 (1), 13–23 (2003).
  • Salama AD , WomerKL, SayeghMH. Clinical transplantation tolerance: many rivers to cross. J. Immunol.178 (9), 5419–5423 (2007).
  • Mirenda V , BertonI, ReadJet al. Modified dendritic cells coexpressing self and allogeneic major histocompatability complex molecules: an efficient way to induce indirect pathway regulation. J. Am. Soc. Nephrol.15 (4), 987–997 (2004).
  • Wang Z , ShufeskyWJ, MontecalvoA, DivitoSJ, LarreginaAT, MorelliAE. In situ targeting of dendritic cells with donor-derived apoptotic cells restrains indirect allorecognition and ameliorates allograft vasculopathy. PLoS ONE4 (3), e4940 (2009).
  • Sakaguchi S , FukumaK, KuribayashiK, MasudaT. Organ-specific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural self-tolerance; deficit of a T cell subset as a possible cause of autoimmune disease. J. Exp. Med.161 (1), 72–87 (1985).
  • Fowell D , MasonD. Evidence that the T cell repertoire of normal rats contains cells with the potential to cause diabetes. Characterization of the CD4+ T cell subset that inhibits this autoimmune potential. J. Exp. Med.177 (3), 627–636 (1993).
  • Hori S , NomuraT, SakaguchiS. Control of regulatory T cell development by the transcription factor Foxp3. Science299 (5609), 1057–1061 (2003).
  • Fontenot JD , GavinMA, RudenskyAY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol.4 (4), 330–336 (2003).
  • Yoshizaki A , MiyagakiT, Di LilloDJet al. Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions. Nature491 (7423), 264–268 (2012).
  • Mauri C , BosmaA. Immune regulatory function of B cells. Annu. Rev. Immunol.30, 221–241 (2012).
  • Powrie F , MasonD. OX-22high CD4+ T cells induce wasting disease with multiple organ pathology: prevention by the OX-22low subset. J. Exp. Med.172 (6), 1701–1708 (1990).
  • Kim JM , RasmussenJP, RudenskyAY. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat. Immunol.8 (2), 191–197 (2007).
  • Levings MK , RoncaroloMG. Phenotypic and functional differences between human CD4+CD25+ and type 1 regulatory T cells. Curr. Top Microbiol. Immunol.293, 303–326 (2005).
  • Wang J , Ioan-FacsinayA, van der VoortEI, HuizingaTW, ToesRE. Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells. Eur. J. Immunol.37 (1), 129–138 (2007).
  • Waldmann H , ChenTC, GracaLet al. Regulatory T cells in transplantation. Semin. Immunol.18 (2), 111–119 (2006).
  • Mizoguchi A , BhanAK. A case for regulatory B cells. J. Immunol.176 (2), 705–710 (2006).
  • Ding Q , YeungM, CamirandGet al. Regulatory B cells are identified by expression of TIM-1 and can be induced through TIM-1 ligation to promote tolerance in mice. J. Clin. Invest.121 (9), 3645–3656 (2011).
  • Maseda D , CandandoKM, SmithSHet al. Peritoneal cavity regulatory B cells (B10 cells) modulate IFN-gamma+CD4+ T cell numbers during colitis development in mice. J. Immunol.191 (5), 2780–2795 (2013).
  • Kalampokis I , YoshizakiA, TedderTF. IL-10-producing regulatory B cells (B10 cells) in autoimmune disease. Arthritis Res. Ther.15 (Suppl.1), S1 (2013).
  • Geissler EK . The ONE study compares cell therapy products in organ transplantation: introduction to a review series on suppressive monocyte-derived cells. Transplant. Res.1 (1), 11 (2012).
  • Leventhal J , AbecassisM, MillerJet al. Chimerism and tolerance without GVHD or engraftment syndrome in HLA-mismatched combined kidney and hematopoietic stem cell transplantation. Sci. Transl. Med.4 (124), 124ra128 (2012).
  • Owen RD . Immunogenetic consequences of vascular anastomoses between Bovine twins. Science102 (2651), 400–401 (1945).
  • Billingham RE , BrentL, MedawarPB. Actively acquired tolerance of foreign cells. Nature172 (4379), 603–606 (1953).
  • Ildstad ST , SachsDH. Reconstitution with syngeneic plus allogeneic or xenogeneic bone marrow leads to specific acceptance of allografts or xenografts. Nature307 (5947), 168–170 (1984).
  • Tomita Y , SachsDH, KhanA, SykesM. Additional monoclonal antibody (mAB) injections can replace thymic irradiation to allow induction of mixed chimerism and tolerance in mice receiving bone marrow transplantation after conditioning with anti-T cell mABs and 3-Gy whole body irradiation. Transplantation61 (3), 469–477 (1996).
  • Wekerle T , KurtzJ, ItoHet al. Allogeneic bone marrow transplantation with co-stimulatory blockade induces macrochimerism and tolerance without cytoreductive host treatment. Nat. Med.6 (4), 464–469 (2000).
  • Huang CA , FuchimotoY, Scheier-DolbergR, MurphyMC, NevilleDM, Jr., SachsDH. Stable mixed chimerism and tolerance using a nonmyeloablative preparative regimen in a large-animal model. J. Clin. Invest.105 (2), 173–181 (2000).
  • Kawai T , CosimiAB, SpitzerTRet al. HLA-mismatched renal transplantation without maintenance immunosuppression. N. Engl. J. Med.358 (4), 353–361 (2008).
  • Mathes DW , ChangJ, HwangBet al. Simultaneous transplantation of hematopoietic stem cells and a vascularized composite allograft leads to tolerance. Transplantation98 (2), 131–138 (2014).
  • Mathes DW , HwangB, GravesSSet al. Tolerance to vascularized composite allografts in canine mixed hematopoietic chimeras. Transplantation92 (12), 1301–1308 (2011).
  • Scandling JD , BusqueS, Dejbakhsh-JonesSet al. Tolerance and chimerism after renal and hematopoietic-cell transplantation. N. Engl. J. Med.358 (4), 362–368 (2008).
  • Spitzer TR , McAfeeSL, DeyBRet al. Nonmyeloablative haploidentical stem-cell transplantation using anti-CD2 monoclonal antibody (MEDI-507)-based conditioning for refractory hematologic malignancies. Transplantation75 (10), 1748–1751 (2003).
  • Takasato M , ErPX, BecroftMet al. Directing human embryonic stem cell differentiation towards a renal lineage generates a self-organizing kidney. Nat. Cell Biol.16 (1), 118–126 (2014).
  • Lui KO , ZangiL, SilvaEAet al. Driving vascular endothelial cell fate of human multipotent Isl1+ heart progenitors with VEGF modified mRNA. Cell Res.23 (10), 1172–1186 (2013).
  • Lippmann ES , AzarinSM, KayJEet al. Derivation of blood-brain barrier endothelial cells from human pluripotent stem cells. Nat. Biotechnol.30 (8), 783–791 (2012).
  • Volk H-D , Blackburn, Exploiting the regulatory T cell repertoire for the induction of tolerance in regenerative medicine. Regen. Med.10 (3), 305–315 (2015).

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