Skip to main content
SpringerLink
Log in
Book cover

Advances in Allogeneic Hematopoietic Stem Cell Transplantation pp 331–368Cite as

Monoclonal Antibody and Receptor Antagonist Therapy for GVHD

  • Chapter

Part of the book series: Cancer Treatment and Research ((CTAR,volume 101))

Abstract

Recent experimental evidence suggests that dysregulation of complex cytokine networks occurring in three sequential steps is responsible for many of the systemic manifestations of acute graft versus host disease (GVHD) (Figure 1). The first step of GVHD pathophysiology begins with the transplant conditioning regimen, which in clinical BMT includes total body irradiation (TBI) and/or chemotherapy. The conditioning is an important variable in the pathogenesis of acute GVHD because it damages and activates host tissues, including intestinal mucosa, liver and skin. Activated host cells then secrete inflammatory cytokines, e.g. tumor necrosis factor (TNF-a) and IL-1. The presence of inflammatory cytokines during this phase may upregulate adhesion molecules and MHC antigens by mature donor T cells in the second step of acute GVHD. This inflammatory context helps to explain the observation that enhanced risk of GVHD after clinical BMT is associated with certain intensive conditioning regimens that cause extensive injury to epithelial and endothelial surfaces and the subsequent release of inflammatory cytokines.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
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

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Carswell EA, Old LJ, Kassel RL, et al. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci. USA. 1975;72: 3666–3670.

    PubMed  CAS  Google Scholar 

  2. Fiers W. Tumor necrosis factor. Characterization at the molecular, cellular and in vivo level. FEBS Letters. 1991;285: 199–212.

    PubMed  CAS  Google Scholar 

  3. Tracey KJ, Vlassara H, Cerami A. Cachetctin/tumor necrosis factor. Lancet 1989;1: 1122–1126.

    PubMed  CAS  Google Scholar 

  4. Deem RL, Shanahan F, Targan SR. Triggered human mucosal T cells release tumor necrosis factor alpha and interferon gamma which kill human colonic epithelial cells. Clin Exp Immonol. 1991;83: 79–84.

    CAS  Google Scholar 

  5. Pober JS. Effects of tumor necrosis factor and related cytokines on vascular endothelial cells. In: Tumor necrosis factor and related cytokines. 1987: 170–184.

    Google Scholar 

  6. Johnson DR, Pober JS. Tumor necrosis factor regulation of major histocompatibility complex gene expression. Immunol Res. 1991;10: 141–155.

    PubMed  CAS  Google Scholar 

  7. Robinet E, Branelle D, Termitjtelen AM, et al. Evidence for tumor necrosis factor-a involvement in the optimal induction of class I allospecific T cells. J Immunol. 1990;144: 4555–4561.

    PubMed  CAS  Google Scholar 

  8. Hogquist KA, Nett MA, E.R. U, Chaplin DD. Interleukin-1 is processed and released during apoptosis. Proc Natl Acad Sci. USA. 1991;88: 8485.

    PubMed  CAS  Google Scholar 

  9. Yuan J, Shaham S, Ledoux S, et al. The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta converting enzyme. Cell 1993;75: 641–652

    PubMed  CAS  Google Scholar 

  10. Kuida K, Lippke JA, Ku G, et al. Altered cytokines export and apoptosis in mice deficient in interleukin-lB converting enzyme. Science 1995;267: 2000–2003.

    PubMed  CAS  Google Scholar 

  11. Miura M, Zhu H, Rotello R, et al. Induction of apoptosis in fibroblasts by IL-1 beta converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3. Cell 1993;75: 653–660.

    PubMed  CAS  Google Scholar 

  12. Itoh N, Yonehara S, Ishii A, et al. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 1991;66: 233–243.

    PubMed  CAS  Google Scholar 

  13. Ju ST, Panka DJ, Cui H, et al. Fas (CD95)/Fas L interactions required for programmed cell death after T cell activation. Nature 1995;373: 444–448.

    PubMed  CAS  Google Scholar 

  14. Nestel FP, Price KS, Seemayer TA, et al. Macrophage priming and lipopolysaccharide-triggered release of tumor necrosis factor alpha during graft-versus-host disease. J Exp Med 1992;175: 405–413.

    PubMed  CAS  Google Scholar 

  15. Niederwieser D, Herold M, Woloszuczuk W, et al. Endogenous IFN-gamma during human bone marrow transplantation. Transplantation 1990;50: 620–625.

    PubMed  CAS  Google Scholar 

  16. Haagmans BL, Stals FS, van der Meide PH, Bruggeman CA, et al. Tumor necrosis factor alpha promotes replication and pathogenicity of rat cytomegalovirus. J Virol 1994;68: 2297–2304.

    PubMed  CAS  Google Scholar 

  17. Hallahan DE, Spriggs DR, Beckett MA, Kufe DW, et al. Increased tumor necrosis factor-a mRNA after cellular exposure to ionizing radiation. Proc Natl Acad Sci USA 1989;86: 10104–10107.

    PubMed  CAS  Google Scholar 

  18. Sherman ML, Datta R, Hallahan DE, et al. Regulation of tumor necrosis factor gene expression by ionizing radiation in human myeloid leukemia cells and peripheral blood monocytes. J Clin Invest 1991;87: 1794–1797.

    PubMed  CAS  Google Scholar 

  19. Iwamoto KS, McBride WH. Production of 13-hydroxyoctadecadienoic acid and tumor necrosis factor-a by murine peritoneal macrophages in response to irradiation. RadiatRes 1994;139: 103–108.

    CAS  Google Scholar 

  20. Hoffman RA, Langrehr JM, Simmons RL. The role of inducible nitric oxide synthetase during graft-versus-host disease. Transplant Proc 1992;24: 2856.

    PubMed  CAS  Google Scholar 

  21. Girinsky TA, Pallardy M, Comoy E, et al. Peripheral blood corticotropin-releasing factor, adrenocorticotropic hormone and cytokine (interleukin beta, interleukin 6, tumor necrosis factor alpha) levels after high-and low-dose total-body irradiation in humans. Radiat Res 1994;139: 360–363.

    PubMed  CAS  Google Scholar 

  22. Xun CQ, Thompson JS, Jennings CD, et al. Effect of total body irradiation, busulfan-cyclophosphamicde, or cyclophosphamide conditioning on inflammatory cytokine release and development of acute and chronic graft-versus-host disease in H-2 incompatible transplanted SCID mice. Blood 1994;83: 2360–2367.

    PubMed  CAS  Google Scholar 

  23. Abhyankar S, Gilliland DG, Ferrara JLM. Interleukin-1 is a critical effector molecule during cytokine dysregulation in graft-versus-host disease to minor histocompatibility antigens. Transplantation 1993;56: 1518–1523.

    PubMed  CAS  Google Scholar 

  24. Hoffman B, Hintermeier-Knabe R, Holler E, et al. Evidence of induction of TNF-alpha by irradiation and cytotoxic therapy preceeding bone marrow transplantation-in vivo and in vitro studies. Networks 1992;3: 257.

    Google Scholar 

  25. Brugger W, Reinhardt D, Galanos C, et al. Inhibition of in-vitro differentiation of human monocytes to macrophages by lipopolysaccharides (LPS); Phenotypic and functional analysis. Intern Immunol 1991:3: 221–227.

    CAS  Google Scholar 

  26. Thomas ED, Ramberg RE, Sale GE, et al. Direct evidence for a bone marrow origin of the alveolar macrophage in man. Science 1976;192: 1016–1018.

    PubMed  CAS  Google Scholar 

  27. Perreault C, Pelletier M,. Belanger R, et al. Persistence of host Langerhans cells following allogeneic bone marrow transplantation: Possible relationship with acute graft-versus-host disease. Br J Haemotol 1985:60: 253–260.

    CAS  Google Scholar 

  28. Barker JN, Mitra RS, Griffith CEM, et al. Keratinocytes as initiators of inflammation. Lancet 1991;337: 211–214.

    PubMed  CAS  Google Scholar 

  29. Walsh LJ, Trincheri F, Waldorf HA, Whitaker D, et al. Human dermal mast cells contain and release tumor necrosis factor alpha which induces enothelial leukocyte adhesion molecule-1. Proc Natl Acad Sci USA 1991;88: 4420–4424.

    Google Scholar 

  30. Murphy GF, Sueki H, Teuscher C, Whitaker D, Korngold R. Role of mast cells in early epithelial target cell injury in experimental acute graft-versus-host disease. J Invest Dermatol 1994;102: 451–461.

    PubMed  CAS  Google Scholar 

  31. Dickinson AM, Sviland L, Dunn J, et al. Demonstration of direct involvement of cytokines in graft-versus-host disease reactions in an in vitro skin explant model. Bone Marrow Transplant 1991;7: 209–216.

    PubMed  CAS  Google Scholar 

  32. Dickinson AM, Sviland L, Jackson G, et al. Monoclonal anti-TNF-alpha suppresses graft-versus-host diesease. J Exp Med 1987;166: 1280–1289.

    Google Scholar 

  33. Piguet PF, Grau GE, Allet B, et al. Tumor necrosis factor/cachetin is an effector of skin and gut lesions of the acute phase of graft-versus-host disease. J Exp Med 1987;166: 1280–1289.

    PubMed  CAS  Google Scholar 

  34. Piguet PF, Grau GE, Vasseli P. Tumor necrosis factor and immunopathology. Immunol Res 1991;10: 122–140.

    PubMed  CAS  Google Scholar 

  35. Shalaby MR, Fendly B, Sheehan KC, et al. Prevention of the graft-versus-host reaction in newborn mice by antibodies to tumor necrosis factor-alpha. Transplantation 1989;47: 1057–1061.

    PubMed  CAS  Google Scholar 

  36. Holler E, Thierfelder S, Nehrends U, et al. Anti-TNF-alpha and pentoxifylline for prophylaxis of a GVHD in murine allogeneic bone marrow transplantation. Oncology 1992;15: 31–35.

    Google Scholar 

  37. Wall DA, Sheehan KC. The role of tumor necrosis factor-alpha and interferon gamma in graft-versus-host disease and related immunodeficiency. Transplantation 1994;57: 273–279.

    PubMed  CAS  Google Scholar 

  38. Allen RD, Staley TA, Sidman CL. Differential cytokine expression in acute and chronic murine graft-versus-host disease. Eur J Immunol 1993;23: 333–337.

    PubMed  CAS  Google Scholar 

  39. Ferrara JL, Abhyankar S, Gilliland DG. Cytokine storm of graft-versus-host disease: a critical effector role for interleukin-1. Transplant Proc 1993;25: 1216–1217.

    PubMed  CAS  Google Scholar 

  40. Lehnert S, WBR Amplification of the graft-versus-host reaction by cyclophosphamide: Dependence on timing of drug administration. Bone Marrow Transplant 1994;13: 473–477.

    PubMed  CAS  Google Scholar 

  41. Zwaan FE, Janson J, Noordijk EM. Graft-versus-host disease limited to area of irradiated skin. Lancet 1980;1: 1081–1082.

    PubMed  CAS  Google Scholar 

  42. Desbarats J, Seemayer TA, Lapp WS. Irradiation of the skin and systemic graft-versus host disease synergize to produce cutaneous lesions. Am J Pathol 1994;144: 883–888.

    PubMed  CAS  Google Scholar 

  43. Holler E, Kold HJ, Moller A, et al. Increased serum levels of tumor necrosis factor alpha precede major complications of bone marrow transplantation. Blood 1990;75: 1011–1016.

    PubMed  CAS  Google Scholar 

  44. Tanaka J, Imamura M, Kasai M, et al. Rapid analysis of tumor necrosis factor-alpha mRNA expression during veno-occlusive disease of the liver after allogeneic bone marrow transplantation. Transplantation 1993;55: 430–432.

    PubMed  CAS  Google Scholar 

  45. Tanaka J, Imamura M, Kasai M, et al. Cytokine gene expression in peripheral blood mononuclear cells during graft-versus-host disease after allogeneic bone marrow transplantation. B J Haematol 1993;85: 558–565.

    CAS  Google Scholar 

  46. Holler E, Kolb HJ, Hintermeier-Knabe R, et al. Involvement of cytokines in graft-versus-host disease and graft-versus-leukemia activity. In: Bergmann L, Mitrou PS, eds. Cytokines in Cancer Therapy. Basel;Karger 1994: 318–329.

    Google Scholar 

  47. Rowbottom AW, Norton J, Riches PG, et al. Cytokine gene expression in skin and lymphoid organs in graft-versus-host disease. J Clin Pathol 1993;46: 341–345.

    PubMed  CAS  Google Scholar 

  48. Holler E, Kolb HJ, Hintermeier-Knabe R, et al. The role of tumor necrosis factor alpha in acute graft-versus-host disease and complications following allogeneic bone marrow transplantation. Transplant Proc 1993;25: 1234–1236.

    PubMed  CAS  Google Scholar 

  49. Holler E, Hinetermeier-Knabe R, Kolb HJ, et al. Low incidence of transplant related complications in patients with chronic release of TNF-alpha before admission to bone marrow transplantation-a clinical correlate of cytokine desensitization. Pathobiology 1991;59: 171–175.

    PubMed  CAS  Google Scholar 

  50. Holler E, Ferrara JLM. Antagonists of Inflammatory Cytokines: Prophylactic and Therapeutic Applications. In: Ferrara JLM, Deeg HJ, Burakoff SJ, ed. Graft-versus-Host Disease. 2nd ed. New York; Marcel Dekker, Inc. 1997;667–692.

    Google Scholar 

  51. Meliconi R, Uguccioni M, Lalli E, et al. Increased serum concentrations of tumor necrosis factor in beta-thalassaemia: Effect of bone marrow transplantation. J Clin Pathol 1992;45: 61–65.

    PubMed  CAS  Google Scholar 

  52. Akhar I, Gold JP, Pan LY, et al. CD4+ B islet cell-reactive T cell clones that suppress autoimmune diabetes in nonobese diabetic mice. J Exp Med 1995;182: 87–97.

    Google Scholar 

  53. Turner DM, Grant SCD, Lamb WR, et al. A genetic marker of high TNF-a production in heart transplant recipients. Transplantation 1995;60: 1113–1117.

    PubMed  CAS  Google Scholar 

  54. Remberger M, Ringden O, Markling L. TNFα levels are increased during bone marrow transplantation conditioning in patients who develop acute GVHD. Bone Marrow Transplant 1995;15: 99–104.

    PubMed  CAS  Google Scholar 

  55. Holler E, Kolb HJ, Hintermeier-Knabe R, et al. Modulation of acute graft-versus-host disease after allogeneic bone marrow transplantation by tumor necrosis factor alpha (TNFα) release in the course of pretransplant conditioning: Role of conditioning regimens and prophylactic application of a monoclonal antibody neutralizing human TNF-alpha (MAK 195F). Blood 1995;86: 890–899.

    PubMed  CAS  Google Scholar 

  56. Almawi WY, Lipman ML, Stevens AC, et al. Abrogation of glucocorticosteroid-mediated inhibition of T cell proliferation by the synergistic action of IL-1, IL-6 and IFNgamma. J Immunol 1991;146: 3523–3527.

    PubMed  CAS  Google Scholar 

  57. Holler E, Kolb HJ, Wilmanns W. Treatment of GVHD-TNF-antibodies and related antagonists. Bone Marrow Transplant. 1993;3: 29–31.

    Google Scholar 

  58. Herve P, Flesch M, Tiberghien P, et al. Phase I-II trial of a monoclonal anti-tumor necrosis factor alpha antibody for the treatment of refractory severe acute graft-versus-host disease. Blood 1992;81: 3362–3368.

    Google Scholar 

  59. Moller A, Emling F, Blohm D, et al. Monoclonal antibodies to human tumour necrosis factor alpha: In vitro and in vivo application. Cytokine 1990;2: 162–169.

    PubMed  CAS  Google Scholar 

  60. Holler E, Kolb HJ, Hintermeier-Knabe R, et al. Systemic release of tumor necrosis factor alpha in human allogeneic bone marrow transplantation: Clinical risk factors, prognostic significance and therapeutic approaches. In: Link, Freund, Schmidt, Welte, eds. Cytokines in Hemapoeisis, Oncology and AIDS II. Berlin-Heidelberg: Springer, 1992: 435–442. Vol II.

    Google Scholar 

  61. Clift RA, Buckner CD, Thomas WI, et al. Marrow transplantation for chronic myeloid leukemia: a randomized study comparing cyclophosmphamide and total body irradiation with busulfan and cyclophosphamide. Blood 1994;84: 2036–2043.

    PubMed  CAS  Google Scholar 

  62. Bianco JJ, Appelbaum FR, Guiffre A, et al. Phase I-II trial of pentoxifylline for the prevention of transplant-related toxicities following bone marrow transplantation. Blood 1991;78: 1205–1211.

    PubMed  CAS  Google Scholar 

  63. Kahls P, Lechner K, Stockschlader M, et al. Pentoxifylline did not prevent transplant-related toxicity in 31 consecutive allogeneic bone marrow transplant recipients. Blood 1992;80: 2683.

    Google Scholar 

  64. Malich U, Tischler HJ, Petersen D, et al. Pentoxifylline and levels of tumor necrosis factor alpha after bone marrow transplantation. In: “19th Annual Meeting of the EBMT”:, ed. Garmisch-Partenkirchen, MMV-Verlag, Munchen. 1993:807.

    Google Scholar 

  65. Eisenberg SP, Evans RJ, Arend WP, et al. Primary structure and functional expression from complementary DNA of a human interleukin-1 receptor antagonist. Nature 1990:343: 341–346.

    PubMed  CAS  Google Scholar 

  66. Arend WP. Interleukin-1 receptor antagonist. Adv Immunol. 1993:54: 167–227.

    PubMed  CAS  Google Scholar 

  67. Granowitz EV, Clark BD, Mancilla J, et al. Interleukin-1 receptor antagonist competitively inhibits the binding of interleukin-1 to the type II interleukin-1 receptor. J Biol Chem 1991;266: 14147–14150.

    PubMed  CAS  Google Scholar 

  68. Arend WP, Welgus HG, Thompson RC, et al. Biological properties of recombinant human monocyte-derived interleukin-1 receptor antagonist. J Clin Invest 1990;85: 16941697.

    Google Scholar 

  69. Haskill S, Martin G, Van Le L, et al. CDNA cloning of an intracellular form of the human interleukin-1 receptor antagonist associated with epithelium. Proc Natl Acad Sci USA 1990;88: 3681–3685.

    Google Scholar 

  70. Aukrust P, Froland S, Liabakk NB, et al. Release of cytokines, soluble cytokine receptors, and interleukin-1 receptor antagonist after intravenous immunoglobin administration in vivo. Blood 1994;84: 2136–2143.

    PubMed  CAS  Google Scholar 

  71. Antin JH, Weinstein HJ, Guinan EC, et al. Recombinant human interleukin-1 receptor antagonist in the treatment of steroid-resistant graft-versus-host disease. Blood 1994;84: 1342–1348.

    PubMed  CAS  Google Scholar 

  72. Echtenacher B, Falk W, Maennel DN, et al. Requirement of endogeneous tumor necrosis factor/cachetin for recovery from experimental peritonitis. J Immunol 1990;145: 3762–3766.

    PubMed  CAS  Google Scholar 

  73. Hill GR, Cooke KR, Teshima T, et al. Interleukin-11 promotes T cell polarization and prevents acute graft-versus-host disease after allogeneic bone marrow transplantation. J Clin Invest 1998;102: 115–123.

    PubMed  CAS  Google Scholar 

  74. Waldmann H, Cobbold S, Hale G. What can be done to prevent graft-verus-host disease? Curr Opin Immunol 1994;6: 777–783.

    PubMed  CAS  Google Scholar 

  75. Truitt R, Johnson B, McCabe C. Graft Versus Leukemia. In: Graft-vs-Host Disease 2nd ed. Ferrara, Deeg, Burkaoff: New York: Marcel Dekker, Inc., 1997: 385–424.

    Google Scholar 

  76. Bearman SI. The syndrome of hapatic veno-occlusive disease after marrow transplantation. Blood 1995;85: 3005–3020.

    PubMed  CAS  Google Scholar 

  77. Glickman E, Jolivet I, Scrobohaci ML, et al. Use of protaglandin E1 for prevention of liver veno-occlusive disease in leukemic patients with allogeneic bone marrow transplantation. Brit J Haematol 1990;74: 277–281.

    Google Scholar 

  78. Cooke KR, Kobzik L, Martin TR, et al. An experimental model of idiopathic pneumonia syndrome after bone marrow transplantation. I. The roles of minor H antigens and endotoxin. Blood 1996;8: 3230–3239.

    Google Scholar 

  79. Piguet PF, Grau GE, Collart MA, Vassalli P, et al. Pneumopathies of the graft-versus-host reaction. Alveolitis associated with an increased level of tumor necrosis factor MRNA and chronic interstitial pneumonitis. Lab Invest 1989;61: 37–45.

    PubMed  CAS  Google Scholar 

  80. Rubin P, Finkelstein J, Shapiro D. Molecular biology mechanisms in radiation induction of pulmonary injury syndromes: Interrelationship between the alveolar macrophage and the septal fibroblast. Int J Radiat Oncol Biol Phys 1992;24: 93–101.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  82. Gross JA, Callas E, Allison JP. Identification and distribution of the costimulatory receptor CD28 in the mouse. J Immunol 1992;149: 380–388.

    PubMed  CAS  Google Scholar 

  83. Linsley PS, Brady W, Urnes M, et al. CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med 1991;174: 561–569.

    PubMed  CAS  Google Scholar 

  84. Linsley PS, Wallace PM, Johnson J, et al. Immunosuppression in vivo by a soluble form of the CTLA-4 T cell activation molecule. Science 1992;257: 792–795.

    PubMed  CAS  Google Scholar 

  85. Lenschow DJ, Zeng Y, Thistlethwaite JR, et al. Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA-4Ig. Science 1992;257: 789–792.

    PubMed  CAS  Google Scholar 

  86. Turka LA, Linsley PS, H.L., et al. T cell activation by the CD28 ligand B7 is required for cardiac allograft rejection in vivo. Proc Natl Acad Sci USA 1992;89: 11102–11105.

    PubMed  CAS  Google Scholar 

  87. Miller SD, Vanderlugt CL, Lenschow DJ, et al. Blockade of CD28/B7-1 interaction prevents epitope spreading and clinical relapses of murine EAE. Immunity 1995;3: 739–745.

    PubMed  CAS  Google Scholar 

  88. Lenschow DJ, Ho SC, Sattar H, et al. Differential effects of anti-B7-l and anti-B7-2 monoclonal antibody treatment on the development of diabetes in the nonobese diabetic mouse. J Exp Med 1995;181: 1145–1155.

    PubMed  CAS  Google Scholar 

  89. Blazar BR, Taylor PA, Linsley PS, et al. In vivo blockade of CD28/CTLA4:B7/BB1 interaction with CTLA4-Ig reduces lethal murine graft-versus host disease across the major histocompatibility complex barrier in mice. Blood 1994;83: 3815–3825.

    PubMed  CAS  Google Scholar 

  90. Wallace PM, Johnson JS, MacMaster JF, et al. CTLA-4Ig treatment ameliorates the lethality of murine graft-versus-host disease across major histocompatibility complex barriers. Transplantation 1994;58: 602–610.

    PubMed  CAS  Google Scholar 

  91. Blazar BR, P.A. T, Gray GS, Vallera DA. The role of T cell subsets in regulating the in vivo efficacy of CTLA4-Ig in preventing graft-versus-host disease in recipients of fully MHC or minor histocompatibility (miH) only disparate donor inocula. Transplantaion 1994;58L1422–1426.

    Google Scholar 

  92. Blazar BR, Sharpe AH, Taylor PA, et al. Infusion of anti-B7.1 (CD80) and anti-B7.2 (CD86) monoclonal antibodies inhibit murine graft-versus-host disease lethality in part via direct effects on CD4+ and CD8+ T cells. J Immunol 1996;157: 3250–3259.

    PubMed  CAS  Google Scholar 

  93. Lenschow DJ, Sperling AI, Cooke MP, et al. Differential up-regulation of the B7-1 and B7-2 costimulatory molecules after Ig receptor engagement by antigen. J Immunol 1994;153: 1990–1997.

    PubMed  CAS  Google Scholar 

  94. Linsley PS, Greene J, Brady W, et al. Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA4 receptors. Immunity 1994;1: 793–801.

    PubMed  CAS  Google Scholar 

  95. Kuchroo VK, Das MP, Brown JA, et al. B7-1 and B7-2 costimulatory molecules activate differentially the Thl/Th2 developmental pathways’.application to autoimmune disease therapy. Cell 1995;80: 707–718.

    PubMed  CAS  Google Scholar 

  96. Freeman GJ, Boussiotis VA, Anumanthan A, et al. B7-1 and B7-2 do not deliver identical costimulatory signals, since B7-2 but not B7-1 preferentially costimulates the initial production of IL-4. Immunity 1995;2: 523–532.

    PubMed  CAS  Google Scholar 

  97. Lenschow DJ. Expression and functional significance of an additional ligand for CTLA-4. Proc Natl Acad Sci USA 1993;90: 11054–11058.

    PubMed  CAS  Google Scholar 

  98. Hathcock KS, Laszlo G, Pucillo C, et al. Comparative analysis of B7-1 and B7-2 costimulatory ligands: expression and function. J Exp Med 1994;180: 631–640.

    PubMed  CAS  Google Scholar 

  99. Azuma M, Yssel H, Phillips JH, et al. Functional expression of B7/BB1 on activated T lymphocytes. J Exp Med 1993;25: 207–211.

    Google Scholar 

  100. Das MRP, Zamvil SS, Bordello F, et al. Reciprocal expression of costimulatory molecules, B7-1 and B7-2, on murine T cells following activation. Eur J Immunol 1995;25: 207–211.

    Google Scholar 

  101. Hirokawa M, Kitabayashi A, Kuroki J, et al. Signal transduction by B7/BB1 induces protein tyrosine phosphorylation and synergizes with signalling through T cell receptor/CD3. Immunol 1995;86: 155–161.

    CAS  Google Scholar 

  102. Sansom DM, Hall ND. B7/BB1, the ligand for CD28 is expressed on repeatedly activated T cells in vitro. Eur J Immunol 1993;23: 295–298.

    PubMed  CAS  Google Scholar 

  103. Racke MK, Scott DE, Quigley L, et al. Distinct role for B7-1 (CD80) and B7-2 (CD86) in the initiation of experimental encephalomyelitis. J Clin Invest 1995;96: 2195–2203.

    PubMed  CAS  Google Scholar 

  104. Sprent J, von Boehmer H. Activation of T lymphocytes to M locus determinants in vivo. I. Quantitation of T cell proliferation and migration into thoracic duct lymph. Eur J Immunol 1976;6: 352–358.

    PubMed  CAS  Google Scholar 

  105. Hakim FT, Cepeda R, Gray GS, et al. Acute graft-versus-host reaction can be aborted by blockade of costimulatory molecules. J Immunol 1995;155: 1757–1766.

    PubMed  CAS  Google Scholar 

  106. Blazar BR, Boyer MW, Taylor PA, et al. The role of CD28:B7 in the persistent graft-vs-leukemia (GVL) effect of delayed post-BMT splenocyte infusions in mice. Blood 1995;86: 115.

    Google Scholar 

  107. Boyer MW, Vallera DA, Taylor PA, et al. The role of B7 costimulation by murine acute myeloid leukemia in the generation and function of a CD8+ T cell line with potent in vivo graft-versus-leukemia properties. Blood 1997;89(9): 3477–3485.

    PubMed  CAS  Google Scholar 

  108. Tan P, Anasetti C, Hansen JA, et al. Induction of alloantigen-speciflc hyporesponsiveness in human T lymphocytes by blocking interaction of CD28 with its natural ligand B7/BB1. J Exp Med 1993;177: 165–173.

    PubMed  CAS  Google Scholar 

  109. Blazar BR, Taylor PA, Panoskaltis-Mortari A, et al. Co-blockade of the LFA1:1CAM and CD28/CTLA4:B7 pathways is a highly effective means of preventing acute lethal graft-versus-host disease induced by fully major histocompatibility complex-disparate donor grafts. Blood 1995;85: 2607–2618.

    PubMed  CAS  Google Scholar 

  110. Lin H, Boiling SF, Linsley PS, et al. Long term acceptance of major histocompatibility complex mismatched cardiac allografts induced by CTLA-4Ig plus donor-specific transfusion. J Exp Med 1993; 178: 1801–1806.

    PubMed  CAS  Google Scholar 

  111. Isobe M, Yagita H, Okumura K, et al. Specific acceptance of cardiac allograft after treatment with antibodies to ICAM-1 and LFA-1. Nature 1992;255: 1125–1127.

    CAS  Google Scholar 

  112. Sligh JE, Ballantyne CM, Rich SS, et al. Inflammatory and immune responses are impaired in mice deficient in intercellular adhesion molecule-1. Proc Natl Acad Sci USA 1993;90: 8529–8533.

    PubMed  CAS  Google Scholar 

  113. Gribben JG, Guinan EC, Boussiotis VA, et al. Complete blockade of B7 family-mediated costimulation is necessary to induce human alloantigen-specific anergy: a method to ameliorate graft-versus-host disease and extend the donor pool. Blood 1996;87: 4887–4893.

    PubMed  CAS  Google Scholar 

  114. Groux H, Bigler M, deVries JE, et al. Interleukin-10 induces a long-term antigen-specific anergic state in human CD4+ T cells. J Exp Med 1996;184: 19–29.

    PubMed  CAS  Google Scholar 

  115. Clark EA, Ledbetter JA. Activation of human B cells mediated through two distinct cell surface differentiation antigens, Bp35 and Bp50. Proc Natl Acad Sci USA 1986;72: 4494–4498.

    Google Scholar 

  116. Hart DNJ, McKenzie JL. Isolation and characterization of human tonsil dendritic cells display a unique antigenic phenotype. J Exp Med 1988;168: 157–170.

    PubMed  CAS  Google Scholar 

  117. Schriever F, Freedman AS, Freeman G, et al. Isolated human follicular dendritic cells display a unique antigenic phenotype. J Exp Med 1989; 169(6): 2043–2058.

    PubMed  CAS  Google Scholar 

  118. Galy AHM, Spits H. CD40 is functionally expressed on human thymic epithelium. J Immunol 1992;149: 775–782.

    PubMed  CAS  Google Scholar 

  119. Hollenbaugh D, Grosmaire LS, Kullas CD, et al. The human T cell antigen p39, a member of the TNF gene family, is a ligand for the CD40 receptor: expression of a soluble form of gp39 with B cell co-stimulatory activity. EMBO J 1992;11: 4313–4321.

    PubMed  CAS  Google Scholar 

  120. Armitage RJ, Fanslow WC, Strockbine L, et al. Molecular and biological characterization of a murine ligand for CD40. Nature 1992;357: 80–82.

    PubMed  CAS  Google Scholar 

  121. Noelle RJ, Roy M, Sheperd DM, et al. A 39 kDa protein on activated helper T cells bind CD40 and transduces the signal for cognate activation of B cells. Proc Natl Acad Sci USA 1992;89: 6550–6554.

    PubMed  CAS  Google Scholar 

  122. Lederman S, Yellin MJ, Inghirami G, et al. Molecular interactions mediating T-B lymphocyte collaboration in human lymphoid follicles; roles of T cell B cell-activating molecule (5c8 antigen) and CD40 in contact-dependent help. J Immunol 1992;149: 3817–3826.

    PubMed  CAS  Google Scholar 

  123. Hermann P, Van-Kooten C, Gaillard C, et al. CD40 ligand postive CD8+ T cell clones allow B cell growth and differentiation. Eur J Immunol 1995;25: 2927–2977.

    Google Scholar 

  124. Grammer AC, Bergman MC, Miura Y, et al. The CD 40 ligand expressed by human B cells costimulates B cell responses. J Immunol 1995;154: 4996–5010.

    PubMed  CAS  Google Scholar 

  125. Ranheim EA, Kipps TJ. Activated T cells induced expression of B7/BBI on normal or leukemic B cells through a CD40-dependent signal. J Exp Med 1993;177: 925–935.

    PubMed  CAS  Google Scholar 

  126. Kennedy MK, Mohler KM, Shanebeck KD, et al. Induction of B cell costimulatory function by recombinant murine CD40. Eur J Immunol 1994;24: 116–123.

    PubMed  CAS  Google Scholar 

  127. Klaus SJ, Pinchuk LM, Ochs HD, et al. Costimulation through CD28 enhances T cell dependent B cell activation via CD40-CD40L interaction. J Immunol 1994;152: 5643–5652.

    PubMed  CAS  Google Scholar 

  128. Ding L, Green JM, Thompson CG, et al. B7/CD28-dependent and-independent induction of CD40 ligand expression. J Immunol 1995;155: 5124–5132.

    PubMed  CAS  Google Scholar 

  129. Jaiswal AL, Dubey C, Swain SL, et al. Regulation of CD40 ligand expression on naive CD4 T cells-a role for TCR but not costimulatory signals. Int Immunol 1996;8: 275–285.

    PubMed  CAS  Google Scholar 

  130. Buhlmann JE, Foy TM, Aruffo A, et al. In the absence of a CD40 signal, B cells are tolerogenic. Immunity 1995;2: 645–653.

    PubMed  CAS  Google Scholar 

  131. Hollander GA, Castigli E, Kulbacki R, et al. Induction of alloantigen-specific tolerance by B cells from CD40 deficient mice. Proc Natl Acad SciUSA 1996;1996: 4994–4998.

    Google Scholar 

  132. Durie FH, Fava RA, Foy TM, et al. Prevention of collagen-induced arthritis with an antibody to gp39, the ligand for CD40. Science 1993;261: 1328–1330.

    PubMed  CAS  Google Scholar 

  133. Gerritse K, Laman JD, Noelle RJ, et al. CD40-CD40 ligand interactions in experimental allergic encephalomyelitis and multiple sclerosis. Proc Natl Acad Sci USA 1996;93: 2499–2504.

    PubMed  CAS  Google Scholar 

  134. Parker DC, Greiner DL, Phillips NE, et al. Survival of mouse pancreatic islet allografts in recipients treated with allogeneic small lymphocytes and antibody CD40 ligand. Proc Natl Acad Sci USA 1995;92: 9560–9564.

    PubMed  CAS  Google Scholar 

  135. Durie FH, Aruffo A, Ledbetter J, et al. Antibody to the ligand of CD40, gp39, blocks the occurrence of the acute and chronic forms of graft-vs-host disease. J Clin Invest 1994;94: 1333–1338.

    PubMed  CAS  Google Scholar 

  136. Blazar BR, Taylor P, Panoskaltsis-Mortari A, et al. Blockade of CD40 Ligand-CD40 Interaction Impairs CD4+ T Cell Mediated Alloreactivity by Inhibiting Mature Donor T Cell Expansion and Function after Bone Marrow Transplantation. J Immunol 1997;158: 29–39.

    PubMed  CAS  Google Scholar 

  137. Blazar BR, Taylor PA, Noelle RJ, et al. CD4+ T cells tolerized ex vivo to host alloantigen by anti-CD40 ligand (CD40L:CD154) antibody lose their graft-versus-host disease lethality capacity but retain nominal antigen responses. J Clin Invest 1998;102: 473–482.

    PubMed  CAS  Google Scholar 

  138. Imura A, Hori T, Imada K, et al. The human OX40/gp34 system directly mediates adhesion of activated T cells to vascular endothelial cells. J Exp Med 1996;1996: 2185–2195.

    Google Scholar 

  139. Baum PR, Gayle RBr, Ramsdell F, et al. Molecular characterization of murine and human OX40/OX40 ligand systems: identification of a human OX40 ligand as the HTLV-1 regulated protein gp34. EMBO J 1994;13: 3992–4001.

    PubMed  CAS  Google Scholar 

  140. Stuber E, Storber W. The T-cell-B-cell interaction via OX40-Ox40L is necessary for the T-cell-dependent humoral immune response. J Exp Med 1996;183: 979–989.

    PubMed  CAS  Google Scholar 

  141. Weinburg AD, Bourdette DN, Sullivan TJ, et al. Selective depletion of myelin-reactive T cells with the anti-OX40 antibody ameliorates autoimmune encephalomyelitis. Nat Med 1996;2: 183–189.

    Google Scholar 

  142. Tittle T, Steinkeler C, Weinberg A, et al. Identification of the T cells causing acute GvHD. FASEB J 1996;10: 1435.

    Google Scholar 

  143. Durie FH. Conversion of chronic graft-versus-host disease to that of the acute phenotype using in vivo administration of an antibody to OX40. FASEB J 1996;10: 1435.

    Google Scholar 

  144. Pollok KE, Kim YJ, Zhou Z, et al. Inducible T cell antigen 4-IBB. Analysis of expression and function. J Immunol 1993;150(3): 771–781.

    PubMed  CAS  Google Scholar 

  145. DeBenedette MA, Chie NR, Pollok KE, et al. Role of 4-IBB ligand in costimulation of T lymphocyte growth and its upregulation on M12 B lymphomas by cAMP. J Exp Med 1995;181: 985–992.

    PubMed  CAS  Google Scholar 

  146. Boise LH, Minn AJ, Noel PJ, et al. CD28 costimulation can promote T cell survival by enhancing the expression of Bcl-xL. Immunity 1995;3: 87–98.

    PubMed  CAS  Google Scholar 

  147. Van Parijs L, Ibraghimov A, Abbas AK. The roles of costimulation and Fas in T cell apoptosis and peripheral tolerance. Immunity 1996;4: 321–328.

    PubMed  Google Scholar 

  148. Yonehara S, Ishii A, Yonehara M. A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor. J Exp Med 1989;163: 1747–1756.

    Google Scholar 

  149. Trauth BC, Klas C, Peters AM, et al. Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science 1989;245: 301–305.

    PubMed  CAS  Google Scholar 

  150. Suda T, Takahashi T, Golstein P, et al. Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Cell 1993;75: 1169–1178.

    PubMed  CAS  Google Scholar 

  151. Suda T, Nagata S. Purification and characterization of the Fas-ligand that induces apoptosis. J Exp Med 1994;179: 873–879.

    PubMed  CAS  Google Scholar 

  152. Ogasawara J, Watanabe-Fu Kunaga R, Adachi M, et al. Lethal effect of the anti-Fas antibody in mice [published erratum appears in Nature 1993;365:568]. Nature 1993;364: 806–809.

    PubMed  CAS  Google Scholar 

  153. Suda T, Tanaka M, Miwa K, et al. Apoptosis of mouse naive T cells induced by recombinant soluble fas ligand and activation-induced resistance to fas ligand. J Immunol 1996;157: 3918–3924.

    PubMed  CAS  Google Scholar 

  154. Watanabe-Fukunaga R, Brannan CI, Copeland NC, et al. Lympho-proliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 1992;356: 314–317.

    PubMed  CAS  Google Scholar 

  155. Takahashi T, Tanaka M, Brannan CI, et al. Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell 1994;76: 969–976.

    PubMed  CAS  Google Scholar 

  156. Rouvier E, Luciani MF, Goldstein P. Fas involvement in Ca(2+)-independent T cell mediated cytotoxicity. J Exp Med 1993;177: 195–200.

    PubMed  CAS  Google Scholar 

  157. Watanabe-Fukunaga R, Braman CI, Itoh N, et al. The cDNA structure, expression and chromosomal assignment of the mouse Fas antigen. J Immunol 1992;148: 1274–1279.

    PubMed  CAS  Google Scholar 

  158. Braum MY, Lowin B, French L, et al. Cytotoxic T cells deficient in both functional fas ligand and perforin show residual cytolytic activity yet lose their capacity to induce lethal acute graft-versus-host disease. J Exp Med 1996;183: 657–661.

    Google Scholar 

  159. Baker MB, Altman NH, Podack ER, et al. The role of cell-mediated cytotoxicity in acute GVHD after MHC-matched allogeneic bone marrow transplantation in mice. J Exp Med 1996;183: 2645–2656.

    PubMed  CAS  Google Scholar 

  160. Via C, Nguyen P, Shustov A, et al. A major role for the Fas pathway in acute graft-versus-host disease. J Immunol 1996;157: 5387–5393.

    PubMed  CAS  Google Scholar 

  161. Baker MB, Riley RL, Podack ER, et al. GVHD-associated lymphoid hypoplasia and B cell dysfunction is dependent upon donor T cell-mediated Fas-ligand function, but not perforin function. Proc Natl Acad Sci USA 1997;94: 1366–1371.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of Michigan Cancer Center, Ann Arbor, MI, 48109

    James L. M. Ferrara M.D.

  2. Regensberg University Hospital, Regensburg, D93042, Germany

    Ernst Holler M.D.

  3. University of Minnesota, Minneapolis, MN, 55455

    Bruce Blazar M.D.

Authors
  1. James L. M. Ferrara M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ernst Holler M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bruce Blazar M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Northwestern University Medical Center, Chicago, USA

    Richard K. Burt  & Mary M. Brush  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer Science+Business Media New York

About this chapter

Cite this chapter

Ferrara, J.L.M., Holler, E., Blazar, B. (1999). Monoclonal Antibody and Receptor Antagonist Therapy for GVHD. In: Burt, R.K., Brush, M.M. (eds) Advances in Allogeneic Hematopoietic Stem Cell Transplantation. Cancer Treatment and Research, vol 101. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4987-1_15

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-4987-1_15

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7264-6

  • Online ISBN: 978-1-4615-4987-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation