Skip to main content

Strategies for the Induction of Tolerance with Monoclonal Antibodies

  • Chapter
  • First Online:
The Immunological Barriers to Regenerative Medicine

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

  • 1086 Accesses

Abstract

The introduction in the organism of tissues expressing foreign genes—ranging from major histocompatibility antigens to the products of gene therapy—have in common their ability to elicit protective immune responses leading to their rejection. Different strategies have been proposed to overcome immune rejection. Monoclonal antibodies, targeting molecules involved in the molecular events required for T cell activation, offer the promise of resetting the immune system toward tolerance without compromising overall immune competence. The mechanisms leading to immune tolerance rely not only on the induction of regulatory T cells, but also on the elimination of aggressive clones, and the triggering of specific gene expression programs that contribute to self-defense of the target tissue.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kaveri SV (2009) Anti-factor VIII antibodies (inhibitors) in hemophilia A: in dire need of basic and therapeutic research. Clin Rev Allergy Immunol 37:55–57

    PubMed  Google Scholar 

  2. Somerfield J, Hill-Cawthorne GA, Lin A et al. A novel strategy to reduce the immunogenicity of biological therapies. J Immunol 185:763–768

    Google Scholar 

  3. Franksson C, Lundgren G, Magnusson G et al (1976) Drainage of thoracic duct lymph in renal transplant patients. Transplantation 21:133–140

    PubMed  CAS  Google Scholar 

  4. Woodruff MF, Anderson NA (1963) Effect of lymphocyte depletion by thoracic duct fistula and administration of antilymphocytic serum on the survival of skin homografts in rats. Nature 200:702

    PubMed  CAS  Google Scholar 

  5. Cosimi AB, Colvin RB, Burton RC et al (1981) Use of monoclonal antibodies to T-cell subsets for immunologic monitoring and treatment in recipients of renal allografts. N Engl J Med 305:308–314

    PubMed  CAS  Google Scholar 

  6. Calne R, Moffatt SD, Friend PJ et al (1999) Campath IH allows low-dose cyclosporine monotherapy in 31 cadaveric renal allograft recipients. Transplantation 68:1613–1616

    PubMed  CAS  Google Scholar 

  7. Graca L, Le Moine A, Cobbold SP et al (2003) Antibody-induced transplantation tolerance: the role of dominant regulation. Immunol Res 28:181–191

    PubMed  CAS  Google Scholar 

  8. Waldmann H, Cobbold SP, Fairchild P et al (2001) Therapeutic aspects of tolerance. Curr Opin Pharmacol 1:392–397

    PubMed  CAS  Google Scholar 

  9. Kahan BD, Rajagopalan PR, Hall M (1999) Reduction of the occurrence of acute cellular rejection among renal allograft recipients treated with basilixiMAb, a chimeric anti-interleukin-2-receptor monoclonal antibody. United States Simulect Renal Study Group. Transplantation 67:276–284

    PubMed  CAS  Google Scholar 

  10. Graca L, Waldmann H (2006) Reprogramming the immune system using antibodies. Methods Mol Biol 333:247–268

    PubMed  CAS  Google Scholar 

  11. Benjamin RJ, Waldmann H (1986) Induction of tolerance by monoclonal antibody therapy. Nature 320:449–451

    PubMed  CAS  Google Scholar 

  12. Gutstein NL, Seaman WE, Scott JH et al (1986) Induction of immune tolerance by administration of monoclonal antibody to L3T4. J Immunol 137:1127–1132

    PubMed  CAS  Google Scholar 

  13. Graca L, Le Moine A, Cobbold SP et al (2003) Dominant transplantation tolerance. Opinion. Curr Opin Immunol 15:499–506

    PubMed  CAS  Google Scholar 

  14. Zheng XX, Sanchez-Fueyo A, Domenig C et al (2003) The balance of deletion and regulation in allograft tolerance. Immunol Rev 196:75–84

    PubMed  CAS  Google Scholar 

  15. Benjamin RJ, Qin SX, Wise MP et al (1988) Mechanisms of monoclonal antibody-facilitated tolerance induction: a possible role for the CD4 (L3T4) and CD11a (LFA-1) molecules in self-non-self discrimination. Eur J Immunol 18:1079–1088

    PubMed  CAS  Google Scholar 

  16. Carteron NL, Wofsy D, Seaman WE (1988) Induction of immune tolerance during administration of monoclonal antibody to L3T4 does not depend on depletion of L3T4+ cells. J Immunol 140:713–716

    PubMed  CAS  Google Scholar 

  17. Qin SX, Wise M, Cobbold SP et al (1990) Induction of tolerance in peripheral T cells with monoclonal antibodies. Eur J Immunol 20:2737–2745

    PubMed  CAS  Google Scholar 

  18. Qin S, Cobbold S, Tighe H et al (1987) CD4 monoclonal antibody pairs for immunosuppression and tolerance induction. Eur J Immunol 17:1159–1165

    PubMed  CAS  Google Scholar 

  19. Marshall SE, Cobbold SP, Davies JD et al (1996) Tolerance and suppression in a primed immune system. Transplantation 62:1614–1621

    PubMed  CAS  Google Scholar 

  20. Chen Z, Cobbold S, Metcalfe S et al (1992) Tolerance in the mouse to major histocompatibility complex-mismatched heart allografts, and to rat heart xenografts, using monoclonal antibodies to CD4 and CD8. Eur J Immunol 22:805–810

    PubMed  CAS  Google Scholar 

  21. Onodera K, Lehmann M, Akalin E et al (1996) Induction of “infectious” tolerance to MHC-incompatible cardiac allografts in CD4 monoclonal antibody-treated sensitized rat recipients. J Immunol 157:1944–1950

    PubMed  CAS  Google Scholar 

  22. Cobbold SP, Castejon R, Adams E et al (2004) Induction of foxP3+ regulatory T cells in the periphery of T cell receptor transgenic mice tolerized to transplants. J Immunol 172:6003–6010

    PubMed  CAS  Google Scholar 

  23. Ford ML, Larsen CP (2009) Translating costimulation blockade to the clinic: lessons learned from three pathways. Immunol Rev 229:294–306

    PubMed  CAS  Google Scholar 

  24. Graca L (2008) CTLA4Ig and the therapeutic potential of T cell co-stimulation blockade. Acta Reumatol Port 33:267–276

    PubMed  Google Scholar 

  25. Kirk AD, Burkly LC, Batty DS et al (1999) Treatment with humanized monoclonal antibody against CD154 prevents acute renal allograft rejection in nonhuman primates. Nat Med 5:686–693

    PubMed  CAS  Google Scholar 

  26. Quezada SA, Jarvinen LZ, Lind EF et al (2004) CD40/CD154 interactions at the interface of tolerance and immunity. Annu Rev Immunol 22:307–328

    PubMed  CAS  Google Scholar 

  27. Kawai T, Andrews D, Colvin RB et al (2000) Thromboembolic complications after treatment with monoclonal antibody against CD40 ligand. Nat Med 6:114

    CAS  Google Scholar 

  28. Adams AB, Shirasugi N, Jones TR et al (2005) Development of a chimeric anti-CD40 monoclonal antibody that synergizes with LEA29Y to prolong islet allograft survival. J Immunol 174:542–550

    PubMed  CAS  Google Scholar 

  29. Bluestone JA, St Clair EW, Turka LA (2006) CTLA4Ig: bridging the basic immunology with clinical application. Immunity 24:233–238

    PubMed  CAS  Google Scholar 

  30. Levisetti MG, Padrid PA, Szot GL et al (1997) Immunosuppressive effects of human CTLA4Ig in a non-human primate model of allogeneic pancreatic islet transplantation. J Immunol 159:5187–5191

    PubMed  CAS  Google Scholar 

  31. Kirk AD, Harlan DM, Armstrong NN et al (1997) CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates. Proc Natl Acad Sci USA 94:8789–8794

    PubMed  CAS  Google Scholar 

  32. Larsen CP, Pearson TC, Adams AB et al (2005) Rational development of LEA29Y (belatacept), a high-affinity variant of CTLA4-Ig with potent immunosuppressive properties. Am J Transplant 5:443–453

    PubMed  CAS  Google Scholar 

  33. Vincenti F, Larsen C, Durrbach A et al (2005) Costimulation blockade with belatacept in renal transplantation. N Engl J Med 353:770–781

    PubMed  CAS  Google Scholar 

  34. Coyle AJ, Lehar S, Lloyd C et al (2000) The CD28-related molecule ICOS is required for effective T cell-dependent immune responses. Immunity 13:95–105

    PubMed  CAS  Google Scholar 

  35. Tafuri A, Shahinian A, Bladt F et al (2001) ICOS is essential for effective T-helper-cell responses. Nature 409:105–109

    PubMed  CAS  Google Scholar 

  36. McAdam AJ, Greenwald RJ, Levin MA et al (2001) ICOS is critical for CD40-mediated antibody class switching. Nature 409:102–105

    PubMed  CAS  Google Scholar 

  37. Dong C, Juedes AE, Temann UA et al (2001) ICOS co-stimulatory receptor is essential for T-cell activation and function. Nature 409:97–101

    PubMed  CAS  Google Scholar 

  38. Iwai H, Kozono Y, Hirose S et al (2002) Amelioration of collagen-induced arthritis by blockade of inducible costimulator-B7 homologous protein costimulation. J Immunol 169:4332–4339

    PubMed  CAS  Google Scholar 

  39. Taylor PA, Panoskaltsis-Mortari A, Freeman GJ et al (2005) Targeting of inducible costimulator (ICOS) expressed on alloreactive T cells down-regulates graft-versus-host disease (GVHD) and facilitates engraftment of allogeneic bone marrow (BM). Blood 105:3372–3380

    PubMed  CAS  Google Scholar 

  40. Guo L, Li XK, Enosawa S et al (2004) Significant enhancement by anti-ICOS antibody of suboptimal tacrolimus immunosuppression in rat liver transplantation. Liver Transpl 10:743–747

    PubMed  Google Scholar 

  41. Peng B, Ye P, Blazar BR et al (2008) Transient blockade of the inducible costimulator pathway generates long-term tolerance to factor VIII after nonviral gene transfer into hemophilia A mice. Blood 112:1662–1672

    PubMed  CAS  Google Scholar 

  42. Graca L, Honey K, Adams E et al (2000) Cutting edge: anti-CD154 therapeutic antibodies induce infectious transplantation tolerance. J Immunol 165:4783–4786

    PubMed  CAS  Google Scholar 

  43. Scully R, Qin S, Cobbold S et al (1994) Mechanisms in CD4 antibody-mediated transplantation tolerance: kinetics of induction, antigen dependency and role of regulatory T cells. Eur J Immunol 24:2383–2392

    PubMed  CAS  Google Scholar 

  44. Graca L, Le Moine A, Lin CY et al (2004) Donor-specific transplantation tolerance: the paradoxical behavior of CD4 + CD25 + T cells. Proc Natl Acad Sci USA 101:10122–10126

    PubMed  CAS  Google Scholar 

  45. Chen ZK, Cobbold SP, Waldmann H et al (1996) Amplification of natural regulatory immune mechanisms for transplantation tolerance. Transplantation 62:1200–1206

    PubMed  CAS  Google Scholar 

  46. Qin S, Cobbold SP, Pope H et al (1993) “Infectious” transplantation tolerance. Science 259:974–977

    PubMed  CAS  Google Scholar 

  47. Davies JD, Leong LY, Mellor A et al (1996) T cell suppression in transplantation tolerance through linked recognition. J Immunol 156:3602–3607

    PubMed  CAS  Google Scholar 

  48. Graca L, Silva-Santos B, Coutinho A (2006) The blind-spot of regulatory T cells. Eur J Immunol 36:802–805

    PubMed  CAS  Google Scholar 

  49. Dorsch S, Roser B (1982) Suppressor cells in transplantation tolerance. I. Analysis of the suppressor status of neonatally and adoptively tolerized rats. Transplantation 33:518–524

    PubMed  CAS  Google Scholar 

  50. Gershon RK, Kondo K (1971) Infectious immunological tolerance. Immunology 21:903–914

    PubMed  CAS  Google Scholar 

  51. Kojima A, Taguchi O, Nishizuka Y (1980) Experimental production of possible autoimmune gastritis followed by macrocytic anemia in athymic nude mice. Lab Invest 42:387–395

    PubMed  CAS  Google Scholar 

  52. Kojima A, Tanaka-Kojima Y, Sakakura T et al (1976) Prevention of postthymectomy autoimmune thyroiditis in mice. Lab Invest 34:601–605

    PubMed  CAS  Google Scholar 

  53. Nishizuka Y, Sakakura T (1969) Thymus and reproduction: sex-linked dysgenesia of the gonad after neonatal thymectomy in mice. Science 166:753–755

    PubMed  CAS  Google Scholar 

  54. Sakaguchi S, Fukuma K, Kuribayashi K et al (1985) 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 161:72–87

    PubMed  CAS  Google Scholar 

  55. Hall BM, Jelbart ME, Gurley KE et al (1985) Specific unresponsiveness in rats with prolonged cardiac allograft survival after treatment with cyclosporine. Mediation of specific suppression by T helper/inducer cells. J Exp Med 162:1683–1694

    PubMed  CAS  Google Scholar 

  56. Fowell D, Mason D (1993) 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 177:627–636

    PubMed  CAS  Google Scholar 

  57. Powrie F, Mason D (1990) OX-22high CD4+ T cells induce wasting disease with multiple organ pathology: prevention by the OX-22low subset. J Exp Med 172:1701–1708

    PubMed  CAS  Google Scholar 

  58. Sakaguchi S, Sakaguchi N, Asano M et al (1995) Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 155:1151–1164

    PubMed  CAS  Google Scholar 

  59. Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299:1057–1061

    PubMed  CAS  Google Scholar 

  60. Fontenot JD, Gavin MA, Rudensky AY (2003) Foxp3 programs the development and function of CD4 + CD25 + regulatory T cells. Nat Immunol 4:330–336

    PubMed  CAS  Google Scholar 

  61. Khattri R, Cox T, Yasayko SA et al (2003) An essential role for Scurfin in CD4 + CD25 + T regulatory cells. Nat Immunol 4:337–342

    PubMed  CAS  Google Scholar 

  62. Chatenoud L (2006) Immune therapies of autoimmune diseases: are we approaching a real cure? Curr Opin Immunol 18:710–717

    PubMed  CAS  Google Scholar 

  63. Waldmann H, Chen TC, Graca L et al (2006) Regulatory T cells in transplantation. Semin Immunol 18:111–119

    PubMed  CAS  Google Scholar 

  64. Graca L, Cobbold SP, Waldmann H (2002) Identification of regulatory T cells in tolerated allografts. J Exp Med 195:1641–1646

    PubMed  CAS  Google Scholar 

  65. Cobbold SP, Adams E, Graca L et al (2006) Immune privilege induced by regulatory T cells in transplantation tolerance. Immunol Rev 213:239–255

    PubMed  CAS  Google Scholar 

  66. Oliveira V, Agua-Doce A, Duarte J et al (2006) Regulatory T cell maintenance of dominant tolerance: induction of tissue self-defense? Transpl Immunol 17:7–10

    PubMed  CAS  Google Scholar 

  67. Fontenot JD, Rasmussen JP, Williams LM et al (2005) Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 22:329–341

    PubMed  CAS  Google Scholar 

  68. Wang J, Ioan-Facsinay A, van der Voort EI et al (2007) Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells. Eur J Immunol 37:129–138

    PubMed  CAS  Google Scholar 

  69. Monteiro M, Almeida C, and Graca L (2010) Identification of regulatory Foxp3+ Invariant NKT cells induced by TGF-beta. J Immunol 105

    Google Scholar 

  70. Levings MK, Roncarolo MG (2005) Phenotypic and functional differences between human CD4 + CD25 + and type 1 regulatory T cells. Curr Top Microbiol Immunol 293:303–326

    PubMed  CAS  Google Scholar 

  71. Kim JM, Rasmussen JP, Rudensky AY (2007) Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat Immunol 8:191–197

    PubMed  CAS  Google Scholar 

  72. Chatila TA, Blaeser F, Ho N et al (2000) JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome. J Clin Invest 106:R75–R81

    PubMed  CAS  Google Scholar 

  73. Liston A, Rudensky AY (2007) Thymic development and peripheral homeostasis of regulatory T cells. Curr Opin Immunol 19:176–185

    PubMed  CAS  Google Scholar 

  74. Graca L, Chen TC, Le Moine A et al (2005) Dominant tolerance: activation thresholds for peripheral generation of regulatory T cells. Trends Immunol 26:130–135

    PubMed  CAS  Google Scholar 

  75. Cobbold SP, Adams E, Graca L et al (2003) Serial analysis of gene expression provides new insights into regulatory T cells. Semin Immunol 15:209–214

    PubMed  CAS  Google Scholar 

  76. Sakaguchi S (2005) Naturally arising Foxp3-expressing CD25 + CD4 + regulatory T cells in immunological tolerance to self and non-self. Nat Immunol 6:345–352

    PubMed  CAS  Google Scholar 

  77. Suvas S, Rouse BT (2006) Treg control of antimicrobial T cell responses. Curr Opin Immunol 18:344–348

    PubMed  CAS  Google Scholar 

  78. Wang HY, Wang RF (2007) Regulatory T cells and cancer. Curr Opin Immunol 19:217–223

    PubMed  CAS  Google Scholar 

  79. Jordan MS, Boesteanu A, Reed AJ et al (2001) Thymic selection of CD4 + CD25 + regulatory T cells induced by an agonist self-peptide. Nat Immunol 2:301–306

    PubMed  CAS  Google Scholar 

  80. Chen TC, Waldmann H, Fairchild PJ (2004) Induction of dominant transplantation tolerance by an altered peptide ligand of the male antigen Dby. J Clin Invest 113:1754–1762

    PubMed  CAS  Google Scholar 

  81. Yates SF, Paterson AM, Nolan KF et al (2007) Induction of regulatory T cells and dominant tolerance by dendritic cells incapable of full activation. J Immunol 179:967–976

    PubMed  CAS  Google Scholar 

  82. Chen W, Jin W, Hardegen N et al (2003) Conversion of peripheral CD4 + CD25- naive T cells to CD4 + CD25 + regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198:1875–1886

    PubMed  CAS  Google Scholar 

  83. Kim JM, Rudensky A (2006) The role of the transcription factor Foxp3 in the development of regulatory T cells. Immunol Rev 212:86–98

    PubMed  CAS  Google Scholar 

  84. Mucida D, Kutchukhidze N, Erazo A et al (2005) Oral tolerance in the absence of naturally occurring tregs. J Clin Invest 115:1923–1933

    PubMed  CAS  Google Scholar 

  85. Apostolou I, von Boehmer H (2004) In vivo instruction of suppressor commitment in naive T cells. J Exp Med 199:1401–1408

    PubMed  CAS  Google Scholar 

  86. Curotto de Lafaille MA, Lino AC, Kutchukhidze N et al (2004) CD25- T cells generate CD25 + Foxp3 + regulatory T cells by peripheral expansion. J Immunol 173:7259–7268

    PubMed  CAS  Google Scholar 

  87. Liang S, Alard P, Zhao Y et al (2005) Conversion of CD4 + CD25- cells into CD4 + CD25 + regulatory T cells in vivo requires B7 costimulation, but not the thymus. J Exp Med 201:127–137

    PubMed  CAS  Google Scholar 

  88. Roncarolo MG, Gregori S, Battaglia M et al (2006) Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunol Rev 212:28–50

    PubMed  CAS  Google Scholar 

  89. Battaglia M, Gregori S, Bacchetta R et al (2006) Tr1 cells: from discovery to their clinical application. Semin Immunol 18:120–127

    PubMed  CAS  Google Scholar 

  90. Lamb JR, Skidmore BJ, Green N et al (1983) Induction of tolerance in influenza virus-immune T lymphocyte clones with synthetic peptides of influenza hemagglutinin. J Exp Med 157:1434–1447

    PubMed  CAS  Google Scholar 

  91. Jenkins MK, Schwartz RH (1987) Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo. J Exp Med 165:302–319

    PubMed  CAS  Google Scholar 

  92. Quill H, Schwartz RH (1987) Stimulation of normal inducer T cell clones with antigen presented by purified Ia molecules in planar lipid membranes: specific induction of a long-lived state of proliferative nonresponsiveness. J Immunol 138:3704–3712

    PubMed  CAS  Google Scholar 

  93. Sloan-Lancaster J, Evavold BD, Allen PM (1993) Induction of T-cell anergy by altered T-cell-receptor ligand on live antigen-presenting cells. Nature 363:156–159

    PubMed  CAS  Google Scholar 

  94. Sloan-Lancaster J, Evavold BD, Allen PM (1994) Th2 cell clonal anergy as a consequence of partial activation. J Exp Med 180:1195–1205

    PubMed  CAS  Google Scholar 

  95. Lombardi G, Hargreaves R, Sidhu S et al (1996) Antigen presentation by T cells inhibits IL-2 production and induces IL-4 release due to altered cognate signals. J Immunol 156:2769–2775

    PubMed  CAS  Google Scholar 

  96. Taams LS, van Rensen AJ, Poelen MC et al (1998) Anergic T cells actively suppress T cell responses via the antigen-presenting cell. Eur J Immunol 28:2902–2912

    PubMed  CAS  Google Scholar 

  97. Qin SX, Cobbold S, Benjamin R et al (1989) Induction of classical transplantation tolerance in the adult. J Exp Med 169:779–794

    PubMed  CAS  Google Scholar 

  98. Alters SE, Shizuru JA, Ackerman J et al (1991) Anti-CD4 mediates clonal anergy during transplantation tolerance induction. J Exp Med 173:491–494

    PubMed  CAS  Google Scholar 

  99. Rammensee HG, Kroschewski R, Frangoulis B (1989) Clonal anergy induced in mature V beta 6+ T lymphocytes on immunizing Mls-1b mice with Mls-1a expressing cells. Nature 339:541–544

    PubMed  CAS  Google Scholar 

  100. Burstein HJ, Shea CM, Abbas AK (1992) Aqueous antigens induce in vivo tolerance selectively in IL-2- and IFN-gamma-producing (Th1) cells. J Immunol 148:3687–3691

    PubMed  CAS  Google Scholar 

  101. Jordan MS, Riley MP, von Boehmer H et al (2000) Anergy and suppression regulate CD4(+) T cell responses to a self peptide. Eur J Immunol 30:136–144

    PubMed  CAS  Google Scholar 

  102. Schonrich G, Momburg F, Hammerling GJ et al (1992) Anergy induced by thymic medullary epithelium. Eur J Immunol 22:1687–1691

    PubMed  CAS  Google Scholar 

  103. Chen Y, Kuchroo VK, Inobe J et al (1994) Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science 265:1237–1240

    PubMed  CAS  Google Scholar 

  104. Graca L (2005) New tools to identify regulatory T cells. Eur J Immunol 35:1678–1680

    PubMed  CAS  Google Scholar 

  105. Hsieh CS, Liang Y, Tyznik AJ et al (2004) Recognition of the peripheral self by naturally arising CD25 + CD4 + T cell receptors. Immunity 21:267–277

    PubMed  CAS  Google Scholar 

  106. Lerman MA, Larkin J 3rd, Cozzo C et al (2004) CD4 + CD25 + regulatory T cell repertoire formation in response to varying expression of a neo-self-antigen. J Immunol 173:236–244

    PubMed  CAS  Google Scholar 

  107. Veldhoen M, Magee AI, Penha-Goncalves MN et al (2005) Transduction of naive CD4 T cells with kinase-deficient Lck-HIV-Tat fusion protein dampens T cell activation and provokes a switch to regulatory function. Eur J Immunol 35:207–216

    PubMed  CAS  Google Scholar 

  108. Curiel TJ, Coukos G, Zou L et al (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10:942–949

    PubMed  CAS  Google Scholar 

  109. Yamashita K, Ollinger R, McDaid J et al (2006) Heme oxygenase-1 is essential for and promotes tolerance to transplanted organs. FASEB J 20:776–778

    PubMed  CAS  Google Scholar 

  110. Gozzelino R, Jeney V, Soares MP Mechanisms of cell protection by heme oxygenase-1. Annu Rev Pharmacol Toxicol 50:323–354

    Google Scholar 

  111. Cobbold SP, Adams E, Farquhar CA et al (2009) Infectious tolerance via the consumption of essential amino acids and mTOR signaling. Proc Natl Acad Sci USA 106:12055–12060

    PubMed  CAS  Google Scholar 

  112. Munn DH, Zhou M, Attwood JT et al (1998) Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 281:1191–1193

    PubMed  CAS  Google Scholar 

  113. Mellor AL, Munn DH (2004) IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol 4:762–774

    PubMed  CAS  Google Scholar 

  114. Mellor AL, Chandler P, Baban B et al (2004) Specific subsets of murine dendritic cells acquire potent T cell regulatory functions following CTLA4-mediated induction of indoleamine 2,3 dioxygenase. Int Immunol 16:1391–1401

    PubMed  CAS  Google Scholar 

  115. Fallarino F, Grohmann U, You S et al (2006) The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells. J Immunol 176:6752–6761

    PubMed  CAS  Google Scholar 

  116. Sykes M (2009) Mechanisms of transplantation tolerance in animals and humans. Transplantation 87:S67–S69

    PubMed  Google Scholar 

  117. Wells AD, Li XC, Li Y et al (1999) Requirement for T-cell apoptosis in the induction of peripheral transplantation tolerance. Nat Med 5:1303–1307

    PubMed  CAS  Google Scholar 

  118. Li Y, Li XC, Zheng XX et al (1999) Blocking both signal 1 and signal 2 of T-cell activation prevents apoptosis of alloreactive T cells and induction of peripheral allograft tolerance. Nat Med 5:1298–1302

    PubMed  CAS  Google Scholar 

  119. Honey K, Cobbold SP, Waldmann H (2000) Dominant tolerance and linked suppression induced by therapeutic antibodies do not depend on Fas-FasL interactions. Transplantation 69:1683–1689

    PubMed  CAS  Google Scholar 

  120. Calne R, Friend P, Moffatt S et al (1998) Prope tolerance, perioperative campath 1H, and low-dose cyclosporin monotherapy in renal allograft recipients. Lancet 351:1701–1702

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Luis Graca .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Graca, L. (2013). Strategies for the Induction of Tolerance with Monoclonal Antibodies. In: Fairchild, P. (eds) The Immunological Barriers to Regenerative Medicine. Stem Cell Biology and Regenerative Medicine. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-5480-9_14

Download citation

Publish with us

Policies and ethics