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CTLA-4-immunoglobulin and indoleamine 2,3-dioxygenase in dominant tolerance

  • Chapter
The Immune Synapse as a Novel Target for Therapy

Part of the book series: Progress in Inflammation Research ((PIR))

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Abstract

The immune system is delicately balanced between self-antigen-driven tolerance and pathogen-driven immunity. In the healthy individual, these two states represent a sliding scale of responsiveness. A shift toward the extreme ends of this scale, i.e., lack of response or an excessive response (such as in autoimmunity and allergy) results in pathophysiological conditions that may be at the basis of diseases. As a consequence, several immune mechanisms have evolved to protect against T and B cells harboring the potential to recognize and become activated by self antigens. Establishment and regulation of self tolerance are exerted at two levels. First, the so-called “central tolerance”, which allows selection of T cells in the thymus (where the gene AIRE permits expression of tissue-specific genes), takes place during T cell development, and contributes to preventing maturation of autoreactive T lymphocytes [1]–[4]. In this process, the majority of self-reactive T cells are deleted by a mechanism termed “negative selection”, but at the same time, some CD4+ T cells differentiate to the CD4+CD25+Foxp3-expressing regulatory T cell (Treg) lineage [5]–[7]. The parameters specifying whether autoreactive CD4+ thymocytes are deleted (recessive tolerance) or differentiate into Tregs (dominant tolerance) remain unclarified.

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References

  1. Goodnow CC, Sprent J, Fazekas de St Groth B, Vinuesa CG (2005) Cellular and genetic mechanisms of self tolerance and autoimmunity. Nature 435: 590–597

    PubMed  CAS  Google Scholar 

  2. Kyewski B, Derbinski J (2004) Self-representation in the thymus: an extended view. Nat Rev Immunol 4: 688–698

    PubMed  CAS  Google Scholar 

  3. Mathis D, Benoist C (2004) Back to central tolerance. Immunity 20: 509–516

    PubMed  CAS  Google Scholar 

  4. Venanzi ES, Benoist C, Mathis D (2004) Good riddance: Thymocyte clonal deletion prevents autoimmunity. Curr Opin Immunol 16: 197–202

    PubMed  CAS  Google Scholar 

  5. Fontenot JD, Rudensky AY (2005) A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat Immunol 6: 331–337

    PubMed  CAS  Google Scholar 

  6. Sakaguchi S (2004) Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 22: 531–562

    PubMed  CAS  Google Scholar 

  7. Sakaguchi S, Setoguchi R, Yagi H, Nomura T (2006) Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in self-tolerance and autoimmune disease. Curr Top Microbiol Immunol 305: 51–66

    PubMed  CAS  Google Scholar 

  8. Filion MC, Proulx C, Bradley AJ, Devine DV, Sekaly RP, Decary F, Chartrand P (1996) Presence in peripheral blood of healthy individuals of autoreactive T cells to a membrane antigen present on bone marrow-derived cells. Blood 88: 2144–2150

    PubMed  CAS  Google Scholar 

  9. Paroli M, Barnaba V (2005) Mechanisms of CD8+ T cell peripheral tolerance to our own antigens. Front Biosci 10: 1628–1634

    PubMed  CAS  Google Scholar 

  10. Saouaf SJ, Brennan PJ, Shen Y, Greene MI (2003) Mechanisms of peripheral immune tolerance: conversion of the immune to the unresponsive phenotype. Immunol Res 28: 193–199

    PubMed  Google Scholar 

  11. Mills KH (2004) Regulatory T cells: friend or foe in immunity to infection? Nat Rev Immunol 4: 841–855

    PubMed  CAS  Google Scholar 

  12. Powrie F, Carlino J, Leach MW, Mauze S, Coffman RL (1996) A critical role for transforming growth factor-beta but not interleukin 4 in the suppression of T helper type 1-mediated colitis by CD45RB(low) CD4+ T cells. J Exp Med 183: 2669–2674

    PubMed  CAS  Google Scholar 

  13. Gavin MA, Rasmussen JP, Fontenot JD, Vasta V, Manganiello VC, Beavo JA, Rudensky AY (2007) Foxp3-dependent programme of regulatory T-cell differentiation. Nature 445: 771–775

    PubMed  CAS  Google Scholar 

  14. 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 

  15. Hori S, Takahashi T, Sakaguchi S (2003) Control of autoimmunity by naturally arising regulatory CD4+ T cells. Adv Immunol 81: 331–371

    PubMed  CAS  Google Scholar 

  16. Bluestone JA, Abbas AK (2003) Natural versus adaptive regulatory T cells. Nat Rev Immunol 3: 253–257

    PubMed  CAS  Google Scholar 

  17. Garba ML, Pilcher CD, Bingham AL, Eron J, Frelinger JA (2002) HIV antigens can induce TGF-beta(1)-producing immunoregulatory CD8+ T cells. J Immunol 168: 2247–2254

    PubMed  CAS  Google Scholar 

  18. Han G, Shao H, Peng Y, Zhang P, Ke Y, Kaplan HJ, Sun D (2007) Suppressor role of rat CD8+CD45RClow T cells in experimental autoimmune uveitis (EAU). J Neuroimmunol 183: 81–88

    PubMed  CAS  Google Scholar 

  19. Sonoda KH, Faunce DE, Taniguchi M, Exley M, Balk S, Stein-Streilein J (2001) NK T cell-derived IL-10 is essential for the differentiation of antigen-specific T regulatory cells in systemic tolerance. J Immunol 166: 42–50

    PubMed  CAS  Google Scholar 

  20. Maloy KJ, Salaun L, Cahill R, Dougan G, Saunders NJ, Powrie F (2003) CD4+CD25+ T(R) cells suppress innate immune pathology through cytokine-dependent mechanisms. J Exp Med 197: 111–119

    PubMed  CAS  Google Scholar 

  21. Houot R, Perrot I, Garcia E, Durand I, Lebecque S (2006) Human CD4+CD25high regulatory T cells modulate myeloid but not plasmacytoid dendritic cells activation. J Immunol 176: 5293–5298

    PubMed  CAS  Google Scholar 

  22. Read S, Greenwald R, Izcue A, Robinson N, Mandelbrot D, Francisco L, Sharpe AH, Powrie F (2006) Blockade of CTLA-4 on CD4+CD25+ regulatory T cells abrogates their function in vivo. J Immunol 177: 4376–4383

    PubMed  CAS  Google Scholar 

  23. Nakamura K, Kitani A, Strober W (2001) Cell contact-dependent immunosuppression by CD4(+)CD25(+) regulatory T cells is mediated by cell surface-bound transforming growth factor beta. J Exp Med 194: 629–644

    PubMed  CAS  Google Scholar 

  24. Belkaid Y, Rouse BT (2005) Natural regulatory T cells in infectious disease. Nat Immunol 6: 353–360

    PubMed  CAS  Google Scholar 

  25. Watanabe N, Wang YH, Lee HK, Ito T, Wang YH, Cao W, Liu YJ (2005) Hassall’s corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature 436: 1181–1185

    PubMed  CAS  Google Scholar 

  26. Steinman RM, Hawiger D, Nussenzweig MC (2003) Tolerogenic dendritic cells. Annu Rev Immunol 21: 685–711

    PubMed  CAS  Google Scholar 

  27. Gad M, Claesson MH, Pedersen AE (2003) Dendritic cells in peripheral tolerance and immunity. APMIS 111: 766–775

    PubMed  CAS  Google Scholar 

  28. Tan JK, O’Neill HC (2005) Maturation requirements for dendritic cells in T cell stimulation leading to tolerance versus immunity. J Leukoc Biol 78: 319–324

    PubMed  CAS  Google Scholar 

  29. Lanzavecchia A, Sallusto F (2001) The instructive role of dendritic cells on T cell responses: lineages, plasticity and kinetics. Curr Opin Immunol 13: 291–298

    PubMed  CAS  Google Scholar 

  30. Mosmann TR, Livingstone AM (2004) Dendritic cells: the immune information management experts. Nat Immunol 5: 564–566

    PubMed  CAS  Google Scholar 

  31. Fallarino F, Grohmann U, Hwang KW, Orabona C, Vacca C, Bianchi R, Belladonna ML, Fioretti MC, Alegre ML, Puccetti P (2003) Modulation of tryptophan catabolism by regulatory T cells. Nat Immunol 4: 1206–1212

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  33. Grohmann U, Fallarino F, Puccetti P (2003) Tolerance, DCs and tryptophan: much ado about IDO. Trends Immunol 24: 242–248

    PubMed  CAS  Google Scholar 

  34. Mellor AL, Munn DH (1999) Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation? Immunol Today 20: 469–473

    PubMed  CAS  Google Scholar 

  35. Sugimoto H, Oda S, Otsuki T, Hino T, Yoshida T, Shir Y (2006) Crystal structure of human indoleamine 2,3-dioxygenase: catalytic mechanism of O2 incorporation by a heme-containing dioxygenase. Proc Natl Acad Sci USA 103: 2611–2616

    PubMed  CAS  Google Scholar 

  36. Munn DH, Zhou M, Attwood JT, Bondarev I, Conway SJ, Marshall B, Brown C, Mellor AL (1998) Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 281: 1191–1193

    PubMed  CAS  Google Scholar 

  37. Shortman K, Heath WR (2001) Immunity or tolerance? That is the question for dendritic cells. Nat Immunol 2: 988–989

    PubMed  CAS  Google Scholar 

  38. Fallarino F, Gizzi S, Mosci P, Grohmann U, Puccetti P (2007) Tryptophan catabolism in IDO+ plasmacytoid dendritic cells. Curr Drug Metab 8: 209–216

    PubMed  CAS  Google Scholar 

  39. Braun D, Longman RS, Albert ML (2005) A two-step induction of indoleamine 2,3 dioxygenase (IDO) activity during dendritic-cell maturation. Blood 106: 2375–2381

    PubMed  CAS  Google Scholar 

  40. Orabona C, Puccetti P, Vacca C, Bicciato S, Luchini A, Fallarino F, Bianchi R, Velardi E, Perruccio K, Velardi A et al (2006) Toward the identification of a tolerogenic signature in IDO-competent dendritic cells. Blood 107: 2846–2854

    PubMed  CAS  Google Scholar 

  41. Grohmann U, Bianchi R, Belladonna ML, Silla S, Fallarino F, Fioretti MC, Puccetti P (2000) IFN-gamma inhibits presentation of a tumor/self peptide by CD8 alpha− dendritic cells via potentiation of the CD8 alpha+ subset. J Immunol 165: 1357–1363

    PubMed  CAS  Google Scholar 

  42. Vacca C, Fallarino F, Perruccio K, Orabona C, Bianchi R, Gizzi S, Velardi A, Fioretti MC, Puccetti P, Grohmann U (2005) CD40 ligation prevents onset of tolerogenic properties in human dendritic cells treated with CTLA-4-Ig. Microbes Infect 7: 1040–1048

    PubMed  CAS  Google Scholar 

  43. Alegre ML, Fallarino F (2006) Mechanisms of CTLA-4-Ig in tolerance induction. Curr Pharm Des 12: 149–160

    PubMed  CAS  Google Scholar 

  44. Fujigaki H, Saito K, Fujigaki S, Takemura M, Sudo K, Ishiguro H, Seishima M (2006) The signal transducer and activator of transcription 1alpha and interferon regulatory factor 1 are not essential for the induction of indoleamine 2,3-dioxygenase by lipopolysaccharide: involvement of p38 mitogen-activated protein kinase and nuclear factor-kappaB pathways, and synergistic effect of several proinflammatory cytokines. J Biochem (Tokyo) 139: 655–662

    CAS  Google Scholar 

  45. Romani L, Bistoni F, Perruccio K, Montagnoli C, Gaziano R, Bozza S, Bonifazi P, Bistoni G, Rasi G, Velardi A et al (2006) Thymosin alpha1 activates dendritic cell tryptophan catabolism and establishes a regulatory environment for balance of inflammation and tolerance. Blood 108: 2265–2274

    PubMed  CAS  Google Scholar 

  46. Fallarino F, Asselin-Paturel C, Vacca C, Bianchi R, Gizzi S, Fioretti MC, Trinchieri G, Grohmann U, Puccetti P (2004) Murine plasmacytoid dendritic cells initiate the immunosuppressive pathway of tryptophan catabolism in response to CD200 receptor engagement. J Immunol 173: 3748–3754

    PubMed  CAS  Google Scholar 

  47. Orabona C, Grohmann U, Belladonna ML, Fallarino F, Vacca C, Bianchi R, Bozza S, Volpi C, Salomon BL, Fioretti MC et al (2004) CD28 induces immunostimulatory signals in dendritic cells via CD80 and CD86. Nat Immunol 5: 1134–1142

    PubMed  CAS  Google Scholar 

  48. Fallarino F, Orabona C, Vacca C, Bianchi R, Gizzi S, Asselin-Paturel C, Fioretti MC, Trinchieri G, Grohmann U, Puccetti P (2005) Ligand and cytokine dependence of the immunosuppressive pathway of tryptophan catabolism in plasmacytoid dendritic cells. Int Immunol 17: 1429–1438

    PubMed  CAS  Google Scholar 

  49. Seo SK, Choi JH, Kim YH, Kang WJ, Park HY, Suh JH, Choi BK, Vinay DS, Kwon BS (2004) 4-1BB-mediated immunotherapy of rheumatoid arthritis. Nat Med 10: 1088–1094

    PubMed  CAS  Google Scholar 

  50. Grohmann U, Volpi C, Fallarino F, Bozza S, Bianchi R, Vacca C, Orabona C, Belladonna ML, Ayroldi E, Nocentini G et al (2007) Reverse signaling through GITR ligand enables dexamethasone to activate IDO in allergy. Nat Med 13: 579–586

    PubMed  CAS  Google Scholar 

  51. Frumento G, Rotondo R, Tonetti M, Damonte G, Benatti U, Ferrara GB (2002) Tryptophan-derived catabolites are responsible for inhibition of T and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase. J Exp Med 196: 459–468

    PubMed  CAS  Google Scholar 

  52. Li Y, Tredget EE, Ghaffari A, Lin X, Kilani RT, Ghahary A (2006) Local expression of indoleamine 2,3-dioxygenase protects engraftment of xenogeneic skin substitute. J Invest Dermatol 126: 128–136

    PubMed  CAS  Google Scholar 

  53. Platten M, Ho PP, Youssef S, Fontoura P, Garren H, Hur EM, Gupta R, Lee LY, Kidd BA, Robinson WH et al (2005) Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite. Science 310: 850–855

    PubMed  CAS  Google Scholar 

  54. Della Chiesa M, Carlomagno S, Frumento G, Balsamo M, Cantoni C, Conte R, Moretta L, Moretta A, Vitale M (2006) The tryptophan catabolite L-kynurenine inhibits the surface expression of NKp46 and NKG2D activating receptors and regulates NK cell function. Blood 108: 4118–4125

    PubMed  Google Scholar 

  55. Fallarino F, Grohmann U, Vacca C, Orabona C, Spreca A, Fioretti MC, Puccetti P (2003) T cell apoptosis by kynurenines. Adv Exp Med Biol 527: 183–190

    PubMed  CAS  Google Scholar 

  56. Fallarino F, Puccetti P (2006) Toll-like receptor 9-mediated induction of the immunosuppressive pathway of tryptophan catabolism. Eur J Immunol 36: 8–11

    PubMed  CAS  Google Scholar 

  57. Brusko TM, Wasserfall CH, Agarwal A, Kapturczak MH, Atkinson MA (2005) An integral role for heme oxygenase-1 and carbon monoxide in maintaining peripheral tolerance by CD4+CD25+ regulatory T cells. J Immunol 174: 5181–5186

    PubMed  CAS  Google Scholar 

  58. Munn DH, Sharma MD, Baban B, Harding HP, Zhang Y, Ron D, Mellor AL (2005) GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase. Immunity 22: 633–642

    PubMed  CAS  Google Scholar 

  59. Bretscher PA (1999) A two-step, two-signal model for the primary activation of precursor helper T cells. Proc Natl Acad Sci USA 96: 185–190

    PubMed  CAS  Google Scholar 

  60. Van Parijs L, Abbas AK (1998) Homeostasis and self-tolerance in the immune system: turning lymphocytes off. Science 280: 243–248

    PubMed  Google Scholar 

  61. Yamada A, Salama AD, Sayegh MH (2002) The role of novel T cell costimulatory pathways in autoimmunity and transplantation. J Am Soc Nephrol 13: 559–575

    PubMed  CAS  Google Scholar 

  62. Collins M, Ling V, Carreno BM (2005) The B7 family of immune-regulatory ligands. Genome Biol 6: 223

    PubMed  Google Scholar 

  63. McAdam AJ, Schweitzer AN, Sharpe AH (1998) The role of B7 co-stimulation in activation and differentiation of CD4+ and CD8+ T cells. Immunol Rev 165: 231–247

    PubMed  CAS  Google Scholar 

  64. 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 

  65. Linsley PS, Greene JL, Tan P, Bradshaw J, Ledbetter JA, Anasetti C, Damle NK (1992) Coexpression and functional cooperation of CTLA-4 and CD28 on activated T lymphocytes. J Exp Med 176: 1595–1604

    PubMed  CAS  Google Scholar 

  66. Linsley PS, Greene JL, Brady W, Bajorath J, Ledbetter JA, Peach R (1994) Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. Immunity 1: 793–801

    PubMed  CAS  Google Scholar 

  67. Greene JL, Leytze GM, Emswiler J, Peach R, Bajorath J, Cosand W, Linsley PS (1996) Covalent dimerization of CD28/CTLA-4 and oligomerization of CD80/CD86 regulate T cell costimulatory interactions. J Biol Chem 271: 26762–26771

    PubMed  CAS  Google Scholar 

  68. Chambers CA, Kuhns MS, Allison JP (1999) Cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates primary and secondary peptide-specific CD4(+) T cell responses. Proc Natl Acad Sci USA 96: 8603–8608

    PubMed  CAS  Google Scholar 

  69. Read S, Malmstrom V, Powrie F (2000) Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J Exp Med 192: 295–302

    PubMed  CAS  Google Scholar 

  70. Jago CB, Yates J, Camara NO, Lechler RI, Lombardi G (2004) Differential expression of CTLA-4 among T cell subsets. Clin Exp Immunol 136: 463–471

    PubMed  CAS  Google Scholar 

  71. Finn PW, He H, Wang Y, Wang Z, Guan G, Listman J, Perkins DL (1997) Synergistic induction of CTLA-4 expression by costimulation with TCR plus CD28 signals mediated by increased transcription and messenger ribonucleic acid stability. J Immunol 158: 4074–4081

    PubMed  CAS  Google Scholar 

  72. Anjos S, Nguyen A, Ounissi-Benkalha H, Tessier MC, Polychronakos C (2002) A common autoimmunity predisposing signal peptide variant of the cytotoxic T-lymphocyte antigen 4 results in inefficient glycosylation of the susceptibility allele. J Biol Chem 277: 46478–46486

    PubMed  CAS  Google Scholar 

  73. Sharpe AH, Freeman GJ (2002) The B7-CD28 superfamily. Nat Rev Immunol 2: 116–126

    PubMed  CAS  Google Scholar 

  74. Stamper CC, Zhang Y, Tobin JF, Erbe DV, Ikemizu S, Davis SJ, Stahl ML, Seehra J, Somers WS, Mosyak L (2001) Crystal structure of the B7-1/CTLA-4 complex that inhibits human immune responses. Nature 410: 608–611

    PubMed  CAS  Google Scholar 

  75. Schwartz JC, Zhang X, Fedorov AA, Nathenson SG, Almo SC (2001) Structural basis for co-stimulation by the human CTLA-4/B7-2 complex. Nature 410: 604–608

    PubMed  CAS  Google Scholar 

  76. Baroja ML, Madrenas J (2003) Viewpoint: therapeutic implications of CTLA-4 compartmentalization. Am J Transplant 3: 919–926

    PubMed  CAS  Google Scholar 

  77. Darlington PJ, Baroja ML, Chau TA, Siu E, Ling V, Carreno BM, Madrenas J (2002) Surface cytotoxic T lymphocyte-associated antigen 4 partitions within lipid rafts and relocates to the immunological synapse under conditions of inhibition of T cell activation. J Exp Med 195: 1337–1347

    PubMed  CAS  Google Scholar 

  78. Chitnis T, Najafian N, Abdallah KA, Dong V, Yagita H, Sayegh MH, Khoury SJ (2001) CD28-independent induction of experimental autoimmune encephalomyelitis. J Clin Invest 107: 575–583

    PubMed  CAS  Google Scholar 

  79. Bachmaier K, Krawczyk C, Kozieradzki I, Kong YY, Sasaki T, Oliveira-dos-Santos A, Mariathasan S, Bouchard D, Wakeham A, Itie A et al (2000) Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-b. Nature 403: 211–216

    PubMed  CAS  Google Scholar 

  80. Li D, Gal I, Vermes C, Alegre ML, Chong AS, Chen L, Shao Q, Adarichev V, Xu X, Koreny T et al (2004) Cutting edge: Cbl-b: one of the key molecules tuning CD28-and CTLA-4-mediated T cell costimulation. J Immunol 173: 7135–7139

    PubMed  CAS  Google Scholar 

  81. Vijayakrishnan L, Slavik JM, Illes Z, Rainbow D, Peterson LB, Sharpe AS, Wicker LS, Kuchroo VK (2005) An autoimmune disease-associated CTLA4 splice variant lacking the B7 binding domain signals negatively in T cells. Novartis Found Symp 267: 200–212; discussion 212–218

    PubMed  CAS  Google Scholar 

  82. Chikuma S, Abbas AK, Bluestone JA (2005) B7-independent inhibition of T cells by CTLA-4. J Immunol 175: 177–181

    PubMed  CAS  Google Scholar 

  83. Thompson CB, Lindsten T, Ledbetter JA, Kunkel SL, Young HA, Emerson SG, Leiden JM, June CH (1989) CD28 activation pathway regulates the production of multiple T-cell-derived lymphokines/cytokines. Proc Natl Acad Sci USA 86: 1333–1337

    PubMed  CAS  Google Scholar 

  84. Lindstein T, June CH, Ledbetter JA, Stella G, Thompson CB (1989) Regulation of lymphokine messenger RNA stability by a surface-mediated T cell activation pathway. Science 244: 339–343

    PubMed  CAS  Google Scholar 

  85. Noel PJ, Boise LH, Green JM, Thompson CB (1996) CD28 costimulation prevents cell death during primary T cell activation. J Immunol 157: 636–642

    PubMed  CAS  Google Scholar 

  86. Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH (1995) Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 3: 541–547

    PubMed  CAS  Google Scholar 

  87. Waterhouse P, Penninger JM, Timms E, Wakeham A, Shahinian A, Lee KP, Thompson CB, Griesser H, Mak TW (1995) Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science 270: 985–988

    PubMed  CAS  Google Scholar 

  88. Brunner MC, Chambers CA, Chan FK, Hanke J, Winoto A, Allison JP (1999) CTLA-4-mediated inhibition of early events of T cell proliferation. J Immunol 162: 5813–5820

    PubMed  CAS  Google Scholar 

  89. Allison JP, Krummel MF (1995) The Yin and Yang of T cell costimulation. Science 270: 932–933

    PubMed  CAS  Google Scholar 

  90. Takahashi S, Kataoka H, Hara S, Yokosuka T, Takase K, Yamasaki S, Kobayashi W, Saito Y, Saito T (2005) In vivo overexpression of CTLA-4 suppresses lymphoproliferative diseases and thymic negative selection. Eur J Immunol 35: 399–407

    PubMed  CAS  Google Scholar 

  91. Mandelbrot DA, McAdam AJ, Sharpe AH (1999) B7-1 or B7-2 is required to produce the lymphoproliferative phenotype in mice lacking cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). J Exp Med 189: 435–440

    PubMed  CAS  Google Scholar 

  92. Tivol EA, Boyd SD, McKeon S, Borriello F, Nickerson P, Strom TB, Sharpe AH (1997) CTLA4Ig prevents lymphoproliferation and fatal multiorgan tissue destruction in CTLA-4-deficient mice. J Immunol 158: 5091–5094

    PubMed  CAS  Google Scholar 

  93. Carreno BM, Bennett F, Chau TA, Ling V, Luxenberg D, Jussif J, Baroja ML, Madrenas J (2000) CTLA-4 (CD152) can inhibit T cell activation by two different mechanisms depending on its level of cell surface expression. J Immunol 165: 1352–1356

    PubMed  CAS  Google Scholar 

  94. Lin H, Rathmell JC, Gray GS, Thompson CB, Leiden JM, Alegre ML (1998) Cytotoxic T lymphocyte antigen 4 (CTLA4) blockade accelerates the acute rejection of cardiac allografts in CD28-deficient mice: CTLA4 can function independently of CD28. J Exp Med 188: 199–204

    PubMed  CAS  Google Scholar 

  95. Grohmann U, Orabona C, Fallarino F, Vacca C, Calcinaro F, Falorni A, Candeloro P, Belladonna ML, Bianchi R, Fioretti MC et al (2002) CTLA-4-Ig regulates tryptophan catabolism in vivo. Nat Immunol 3: 1097–1101

    PubMed  CAS  Google Scholar 

  96. Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD (2002) Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 3: 991–998

    PubMed  CAS  Google Scholar 

  97. Pardoll D (2003) Does the immune system see tumors as foreign or self? Annu Rev Immunol 21: 807–839

    PubMed  CAS  Google Scholar 

  98. Widner B, Sepp N, Kowald E, Ortner U, Wirleitner B, Fritsch P, Baier-Bitterlich G, Fuchs D (2000) Enhanced tryptophan degradation in systemic lupus erythematosus. Immunobiology 201: 621–630

    PubMed  CAS  Google Scholar 

  99. Forrest CM, Kennedy A, Stone TW, Stoy N, Darlington LG (2003) Kynurenine and neopterin levels in patients with rheumatoid arthritis and osteoporosis during drug treatment. Adv Exp Med Biol 527: 287–295

    PubMed  CAS  Google Scholar 

  100. Boasso A, Herbeuval JP, Hardy AW, Anderson SA, Dolan MJ, Fuchs D, Shearer GM (2006) HIV-1 inhibits CD4+ T cell proliferation by inducing indoleamine 2,3-dioxygenase in plasmacytoid dendritic cells. Blood 109: 3351–3359

    PubMed  Google Scholar 

  101. Roncarolo MG, Bacchetta R, Bordignon C, Narula S, Levings MK (2001) Type 1 T regulatory cells. Immunol Rev 182: 68–79

    PubMed  CAS  Google Scholar 

  102. Serafini P, De Santo C, Marigo I, Cingarlini S, Dolcetti L, Gallina G, Zanovello P, Bronte V (2004) Derangement of immune responses by myeloid suppressor cells. Cancer Immunol Immunother 53: 64–72

    PubMed  CAS  Google Scholar 

  103. Lenschow DJ, Zeng Y, Thistlethwaite JR, Montag A, Brady W, Gibson MG, Linsley PS, Bluestone JA (1992) Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4lg. Science 257: 789–792

    PubMed  CAS  Google Scholar 

  104. Turka LA, Linsley PS, Lin H, Brady W, Leiden JM, Wei RQ, Gibson ML, Zheng XG, Myrdal S, Gordon D et al (1992) T-cell activation by the CD28 ligand B7 is required for cardiac allograft rejection in vivo. Proc Natl Acad Sci USA 89: 11102–11105

    PubMed  CAS  Google Scholar 

  105. Azuma H, Chandraker A, Nadeau K, Hancock WW, Carpenter CB, Tilney NL, Sayegh MH (1996) Blockade of T-cell costimulation prevents development of experimental chronic renal allograft rejection. Proc Natl Acad Sci USA 93: 12439–12444

    PubMed  CAS  Google Scholar 

  106. Wekerle T, Kurtz J, Ito H, Ronquillo JV, Dong V, Zhao G, Shaffer J, Sayegh MH, Sykes M (2000) Allogeneic bone marrow transplantation with co-stimulatory blockade induces macrochimerism and tolerance without cytoreductive host treatment. Nat Med 6: 464–469

    PubMed  CAS  Google Scholar 

  107. Larsen CP, Elwood ET, Alexander DZ, Ritchie SC, Hendrix R, Tucker-Burden C, Cho HR, Aruffo A, Hollenbaugh D, Linsley PS et al (1996) Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways. Nature 381: 434–438

    PubMed  CAS  Google Scholar 

  108. Russell ME, Hancock WW, Akalin E, Wallace AF, Glysing-Jensen T, Willett TA, Sayegh MH (1996) Chronic cardiac rejection in the LEW to F344 rat model. Blockade of CD28-B7 costimulation by CTLA4Ig modulates T cell and macrophage activation and attenuates arteriosclerosis. J Clin Invest 97: 833–838

    PubMed  CAS  Google Scholar 

  109. Chandraker A, Azuma H, Nadeau K, Carpenter CB, Tilney NL, Hancock WW, Sayegh MH (1998) Late blockade of T cell costimulation interrupts progression of experimental chronic allograft rejection. J Clin Invest 101: 2309–2318

    PubMed  CAS  Google Scholar 

  110. Levisetti MG, Padrid PA, Szot GL, Mittal N, Meehan SM, Wardrip CL, Gray GS, Bruce DS, Thistlethwaite JR Jr, Bluestone JA (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 

  111. Kirk AD, Harlan DM, Armstrong NN, Davis TA, Dong Y, Gray GS, Hong X, Thomas D, Fechner JH Jr, Knechtle SJ (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 

  112. Vincenti F (2005) Chronic induction. What’s new in the pipeline. Contrib Nephrol 146: 22–29

    PubMed  Google Scholar 

  113. Larsen CP, Pearson TC, Adams AB, Tso P, Shirasugi N, Strobertm E, Anderson D, Cowan S, Price K, Naemura J 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 

  114. Adams AB, Shirasugi N, Durham MM, Strobert E, Anderson D, Rees P, Cowan S, Xu H, Blinder Y, Cheung M et al (2002) Calcineurin inhibitor-free CD28 blockade-based protocol protects allogeneic islets in nonhuman primates. Diabetes 51: 265–270

    PubMed  CAS  Google Scholar 

  115. Abrams JR, Lebwohl MG, Guzzo CA, Jegasothy BV, Goldfarb MT, Goffe BS, Menter A, Lowe NJ, Krueger G, Brown MJ et al (1999) CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris. J Clin Invest 103: 1243–1252

    PubMed  CAS  Google Scholar 

  116. Weinblatt M, Combe B, Covucci A, Aranda R, Becker JC, Keystone E (2006) Safety of the selective costimulation modulator abatacept in rheumatoid arthritis patients receiving background biologic and nonbiologic disease-modifying antirheumatic drugs: A one-year randomized, placebo-controlled study. Arthritis Rheum 54: 2807–2816

    PubMed  CAS  Google Scholar 

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  1. Department of Experimental Medicine, University of Perugia, 06126, Perugia, Italy

    Francesca Fallarino, Carmine Vacca, Claudia Volpi, Maria T. Pallotta, Stefania Gizzi, Ursula Grohmann & Paolo Puccetti

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  1. Francesca Fallarino
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  2. Carmine Vacca
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  1. Unidade de Imunologia Celular Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Professor Egas Moniz, 1649-208, Lisboa, Portugal

    Luis Graca

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Fallarino, F. et al. (2008). CTLA-4-immunoglobulin and indoleamine 2,3-dioxygenase in dominant tolerance. In: Graca, L. (eds) The Immune Synapse as a Novel Target for Therapy. Progress in Inflammation Research. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-8296-4_7

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