Skip to main content
SpringerLink
Log in

Graft Versus Host Disease (GVHD)

  • Chapter
  • First Online:
Immunology of the Skin

  • 2133 Accesses

Abstract

Graft-versus-host disease (GVHD), the major complication of allogeneic hematopoietic cell transplantation (HCT), remains lethal and limits the use of this therapy. Acute GVHD and chronic GVHD involve distinct pathological processes. Acute GVHD has strong inflammatory components, whereas chronic GVHD displays more autoimmune and fibrotic features. Acute GVHD begins with tissue damage to the recipient by conditioning regimens that release pro-inflammatory cytokines and gut bacteria and activate antigen-presenting cells (APCs). Following antigen presentation, a strong cytokine response is initiated, promoting greater antigen presentation and recruitment of effector T cells, and innate immune cells further contributing to the inflammatory cytokine milieu. Finally, effector T cells, NK cells, and pro-inflammatory cytokines will result in end-organ damage, clinically recognized as acute GVHD in the skin, gut, and liver. In contrast, one of the hallmarks to chronic GVHD includes damage to the thymus that is associated with the conditioning regimen and the acute GVHD resulting in decreased negative selection of alloreactive CD4 T cells. Dysregulation of B cells has also been implicated as another hallmark that leads to emergence of autoreactive B cells and production of autoreactive antibodies. It has also been proposed that Th2 cytokine pattern deviation may be involved that induces release of fibrogenic cytokines and macrophage activation followed by tissue fibroblast proliferation and activation. These will result in an autoimmune-like systemic syndrome that is mainly associated with fibroproliferative changes and that can occur in almost any organ in the body. In this chapter, we review the recent advances in understanding the pathophysiology of GVHD as well as its diagnosis.

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

Access this chapter

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 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
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. Antin JH et al (1994) Recombinant human interleukin-1 receptor antagonist in the treatment of steroid-resistant graft-versus-host disease. Blood 84(4):1342–1348

    CAS  PubMed  Google Scholar 

  2. Asai O et al (1998) Suppression of graft-versus-host disease and amplification of graft-versus-tumor effects by activated natural killer cells after allogeneic bone marrow transplantation. J Clin Invest 101(9):1835–1842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Baker MB, Altman NH, Podack ER, Levy RB (1996) The role of cell-mediated cytotoxicity in acute GVHD after MHC-matched allogeneic bone marrow transplantation in mice. J Exp Med 183(6):2645–2656

    Article  CAS  PubMed  Google Scholar 

  4. Beelen DW, Elmaagacli A, Muller KD, Hirche H, Schaefer UW (1999) Influence of intestinal bacterial decontamination using metronidazole and ciprofloxacin or ciprofloxacin alone on the development of acute graft-versus-host disease after marrow transplantation in patients with hematologic malignancies: final results and long-term follow-up of an open-label prospective randomized trial. Blood 93(10):3267–3275

    CAS  PubMed  Google Scholar 

  5. Beelen DW et al (1992) Evidence that sustained growth suppression of intestinal anaerobic bacteria reduces the risk of acute graft-versus-host disease after sibling marrow transplantation. Blood 80(10):2668–2676

    CAS  PubMed  Google Scholar 

  6. Billingham RE (1966) The biology of graft-versus-host reactions. Harvey Lect 62:21–78

    PubMed  Google Scholar 

  7. Blazar BR, Murphy WJ, Abedi M (2012) Advances in graft-versus-host disease biology and therapy. Nat Rev Immunol 12(6):443–458

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Braun MY, Lowin B, French L, Acha-Orbea H, Tschopp J (1996) 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 183(2):657–661

    Article  CAS  PubMed  Google Scholar 

  9. Brok HP, Heidt PJ, van der Meide PH, Zurcher C, Vossen JM (1993) Interferon-gamma prevents graft-versus-host disease after allogeneic bone marrow transplantation in mice. J Immunol 151(11):6451–6459

    CAS  PubMed  Google Scholar 

  10. Brown GR, Lee E, Thiele DL (2002) TNF-TNFR2 interactions are critical for the development of intestinal graft-versus-host disease in MHC class II-disparate (C57BL/6J-->C57BL/6J x bm12)F1 mice. J Immunol 168(6):3065–3071

    Article  CAS  PubMed  Google Scholar 

  11. Calcaterra C et al (2008) Critical role of TLR9 in acute graft-versus-host disease. J Immunol 181(9):6132–6139

    Article  CAS  PubMed  Google Scholar 

  12. Carlens S et al (1998) Risk factors for chronic graft-versus-host disease after bone marrow transplantation: a retrospective single centre analysis. Bone Marrow Transplant 22(8):755–761

    Article  CAS  PubMed  Google Scholar 

  13. Carlson MJ et al (2009) In vitro-differentiated TH17 cells mediate lethal acute graft-versus-host disease with severe cutaneous and pulmonary pathologic manifestations. Blood 113(6):1365–1374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Cavet J et al (2001) Interferon-gamma and interleukin-6 gene polymorphisms associate with graft-versus-host disease in HLA-matched sibling bone marrow transplantation. Blood 98(5):1594–1600

    Article  CAS  PubMed  Google Scholar 

  15. Chakraverty R et al (2006) An inflammatory checkpoint regulates recruitment of graft-versus-host reactive T cells to peripheral tissues. J Exp Med 203(8):2021–2031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Chu YW, Gress RE (2008) Murine models of chronic graft-versus-host disease: insights and unresolved issues. Biol Blood Marrow Transplant 14(4):365–378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Clark FJ et al (2004) Chronic graft-versus-host disease is associated with increased numbers of peripheral blood CD4+CD25high regulatory T cells. Blood 103(6):2410–2416

    Article  CAS  PubMed  Google Scholar 

  18. Clift RA et al (1990) Allogeneic marrow transplantation in patients with acute myeloid leukemia in first remission: a randomized trial of two irradiation regimens. Blood 76(9):1867–1871

    CAS  PubMed  Google Scholar 

  19. Clift RA et al (1994) Marrow transplantation for chronic myeloid leukemia: a randomized study comparing cyclophosphamide and total body irradiation with busulfan and cyclophosphamide. Blood 84(6):2036–2043

    CAS  PubMed  Google Scholar 

  20. Cohen JL, Trenado A, Vasey D, Klatzmann D, Salomon BL (2002) CD4(+)CD25(+) immunoregulatory T cells: new therapeutics for graft-versus-host disease. J Exp Med 196(3):401–406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Cooke KR et al (2001) LPS antagonism reduces graft-versus-host disease and preserves graft-versus-leukemia activity after experimental bone marrow transplantation. J Clin Invest 107(12):1581–1589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Cooke KR et al (1998) Tumor necrosis factor- alpha production to lipopolysaccharide stimulation by donor cells predicts the severity of experimental acute graft-versus-host disease. J Clin Invest 102(10):1882–1891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Cowen EW (2012) Graft-versus-host disease. In: Goldsmith LA, Katz SI, Gilchrest BA et al (eds) Fitzpatrick’s dermatology in general medicine, vol 1, 8th edn. Mc Graw Hill, New York, pp 316–329

    Google Scholar 

  24. Cutler C et al (2006) Rituximab for steroid-refractory chronic graft-versus-host disease. Blood 108(2):756–762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Desbarats J, Lapp WS (1993) Thymic selection and thymic major histocompatibility complex class II expression are abnormal in mice undergoing graft-versus-host reactions. J Exp Med 178(3):805–814

    Article  CAS  PubMed  Google Scholar 

  26. Duffner UA et al (2004) Host dendritic cells alone are sufficient to initiate acute graft-versus-host disease. J Immunol 172(12):7393–7398

    Article  CAS  PubMed  Google Scholar 

  27. Elmaagacli AH et al (2006) Mutations in innate immune system NOD2/CARD 15 and TLR-4 (Thr399Ile) genes influence the risk for severe acute graft-versus-host disease in patients who underwent an allogeneic transplantation. Transplantation 81(2):247–254

    Article  CAS  PubMed  Google Scholar 

  28. Ferrara JL, Deeg HJ (1991) Graft-versus-host disease. N Engl J Med 324(10):667–674

    Article  CAS  PubMed  Google Scholar 

  29. Ferrara JL, Levine JE, Reddy P, Holler E (2009) Graft-versus-host disease. Lancet 373(9674):1550–1561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ferrara JL, Marion A, McIntyre JF, Murphy GF, Burakoff SJ (1986) Amelioration of acute graft vs host disease due to minor histocompatibility antigens by in vivo administration of anti-interleukin 2 receptor antibody. J Immunol 137(6):1874–1877

    CAS  PubMed  Google Scholar 

  31. Ferrara JL, Reddy P (2006) Pathophysiology of graft-versus-host disease. Semin Hematol 43(1):3–10

    Article  CAS  PubMed  Google Scholar 

  32. Filipovich AH et al (2005) National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 11(12):945–956

    Article  PubMed  Google Scholar 

  33. Fowler DH, Kurasawa K, Smith R, Eckhaus MA, Gress RE (1994) Donor CD4-enriched cells of Th2 cytokine phenotype regulate graft-versus-host disease without impairing allogeneic engraftment in sublethally irradiated mice. Blood 84(10):3540–3549

    CAS  PubMed  Google Scholar 

  34. Friedman KJ, LeBoit PE, Farmer ER (1988) Acute follicular graft-vs-host reaction. A distinct clinicopathologic presentation. Arch Dermatol 124(5):688–691

    Article  CAS  PubMed  Google Scholar 

  35. Fujii H et al (2008) Biomarkers in newly diagnosed pediatric-extensive chronic graft-versus-host disease: a report from the Children’s Oncology Group. Blood 111(6):3276–3285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Fukushi N et al (1990) Thymus: a direct target tissue in graft-versus-host reaction after allogeneic bone marrow transplantation that results in abrogation of induction of self-tolerance. Proc Natl Acad Sci U S A 87(16):6301–6305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Gale RP, Reisner Y (1986) Graft rejection and graft-versus-host disease: mirror images. Lancet 1(8496):1468–1470

    Article  CAS  PubMed  Google Scholar 

  38. Ghayur T, Seemayer TA, Xenocostas A, Lapp WS (1988) Complete sequential regeneration of graft-vs.-host-induced severely dysplastic thymuses. Implications for the pathogenesis of chronic graft-vs.-host disease. Am J Pathol 133(1):39–46

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Graubert TA, Russell JH, Ley TJ (1996) The role of granzyme B in murine models of acute graft-versus-host disease and graft rejection. Blood 87(4):1232–1237

    CAS  PubMed  Google Scholar 

  40. Hattori K et al (1998) Differential effects of anti-Fas ligand and anti-tumor necrosis factor alpha antibodies on acute graft-versus-host disease pathologies. Blood 91(11):4051–4055

    CAS  PubMed  Google Scholar 

  41. Herve P et al (1992) 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 79(12):3362–3368

    CAS  PubMed  Google Scholar 

  42. Herve P et al (1990) Treatment of corticosteroid resistant acute graft-versus-host disease by in vivo administration of anti-interleukin-2 receptor monoclonal antibody (B-B10). Blood 75(4):1017–1023

    CAS  PubMed  Google Scholar 

  43. Hill GR et al (1997) Total body irradiation and acute graft-versus-host disease: the role of gastrointestinal damage and inflammatory cytokines. Blood 90(8):3204–3213

    CAS  PubMed  Google Scholar 

  44. Hill GR, Ferrara JL (2000) The primacy of the gastrointestinal tract as a target organ of acute graft-versus-host disease: rationale for the use of cytokine shields in allogeneic bone marrow transplantation. Blood 95(9):2754–2759

    CAS  PubMed  Google Scholar 

  45. Hill GR et al (1999) Differential roles of IL-1 and TNF-alpha on graft-versus-host disease and graft versus leukemia. J Clin Invest 104(4):459–467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Hoffmann P, Ermann J, Edinger M, Fathman CG, Strober S (2002) Donor-type CD4(+)CD25(+) regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation. J Exp Med 196(3):389–399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Hollander GA, Widmer B, Burakoff SJ (1994) Loss of normal thymic repertoire selection and persistence of autoreactive T cells in graft vs host disease. J Immunol 152(4):1609–1617

    CAS  PubMed  Google Scholar 

  48. Holler E et al (1995) Modulation of acute graft-versus-host-disease after allogeneic bone marrow transplantation by tumor necrosis factor alpha (TNF alpha) 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 86(3):890–899

    CAS  PubMed  Google Scholar 

  49. Holler E et al (1990) Increased serum levels of tumor necrosis factor alpha precede major complications of bone marrow transplantation. Blood 75(4):1011–1016

    CAS  PubMed  Google Scholar 

  50. Holler E et al (2004) Both donor and recipient NOD2/CARD15 mutations associate with transplant-related mortality and GvHD following allogeneic stem cell transplantation. Blood 104(3):889–894

    Article  CAS  PubMed  Google Scholar 

  51. Horn TD (1994) Acute cutaneous eruptions after marrow ablation: roses by other names? J Cutan Pathol 21(5):385–392

    Article  CAS  PubMed  Google Scholar 

  52. Hossain MS et al (2011) Flagellin, a TLR5 agonist, reduces graft-versus-host disease in allogeneic hematopoietic stem cell transplantation recipients while enhancing antiviral immunity. J Immunol 187(10):5130–5140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Hymes SR, Alousi AM, Cowen EW (2012) Graft-versus-host disease: part I. Pathogenesis and clinical manifestations of graft-versus-host disease. J Am Acad Dermatol 66(4):515.e511–515.e518; quiz 533 – 514

    Article  Google Scholar 

  54. Imado T et al (2010) The protective role of host Toll-like receptor-4 in acute graft-versus-host disease. Transplantation 90(10):1063–1070

    Article  CAS  PubMed  Google Scholar 

  55. Jones JM, Wilson R, Bealmear PM (1971) Mortality and gross pathology of secondary disease in germfree mouse radiation chimeras. Radiat Res 45(3):577–588

    Article  CAS  PubMed  Google Scholar 

  56. Kappel LW et al (2009) IL-17 contributes to CD4-mediated graft-versus-host disease. Blood 113(4):945–952

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Kernan NA et al (1986) Clonable T lymphocytes in T cell-depleted bone marrow transplants correlate with development of graft-v-host disease. Blood 68(3):770–773

    CAS  PubMed  Google Scholar 

  58. Korngold R, Sprent J (1978) Lethal graft-versus-host disease after bone marrow transplantation across minor histocompatibility barriers in mice. Prevention by removing mature T cells from marrow. J Exp Med 148(6):1687–1698

    Article  CAS  PubMed  Google Scholar 

  59. Korngold R, Sprent J (1985) Surface markers of T cells causing lethal graft-vs-host disease to class I vs class II H-2 differences. J Immunol 135(5):3004–3010

    CAS  PubMed  Google Scholar 

  60. Koyama M et al (2012) Recipient nonhematopoietic antigen-presenting cells are sufficient to induce lethal acute graft-versus-host disease. Nat Med 18(1):135–142

    Article  CAS  Google Scholar 

  61. Kumaki S et al (1998) Prolonged secretion of IL-15 in patients with severe forms of acute graft-versus-host disease after allogeneic bone marrow transplantation in children. Int J Hematol 67(3):307–312

    Article  CAS  PubMed  Google Scholar 

  62. Laughlin MJ et al (2004) Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med 351(22):2265–2275

    Article  CAS  PubMed  Google Scholar 

  63. Lerner KG et al (1974) Histopathology of graft-vs.-host reaction (GvHR) in human recipients of marrow from HL-A-matched sibling donors. Transplant Proc 6(4):367–371

    CAS  PubMed  Google Scholar 

  64. Li H et al (2011) Graft-versus-host disease is independent of innate signaling pathways triggered by pathogens in host hematopoietic cells. J Immunol 186(1):230–241

    Article  CAS  PubMed  Google Scholar 

  65. Lin MT et al (2005) Genetic variation in the IL-10 pathway modulates severity of acute graft-versus-host disease following hematopoietic cell transplantation: synergism between IL-10 genotype of patient and IL-10 receptor beta genotype of donor. Blood 106(12):3995–4001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. MacDonald KP et al (2007) Effector and regulatory T-cell function is differentially regulated by RelB within antigen-presenting cells during GVHD. Blood 109(11):5049–5057

    Article  CAS  PubMed  Google Scholar 

  67. Markey KA et al (2009) Conventional dendritic cells are the critical donor APC presenting alloantigen after experimental bone marrow transplantation. Blood 113(22):5644–5649

    Article  CAS  PubMed  Google Scholar 

  68. Marra DE, McKee PH, Nghiem P (2004) Tissue eosinophils and the perils of using skin biopsy specimens to distinguish between drug hypersensitivity and cutaneous graft-versus-host disease. J Am Acad Dermatol 51(4):543–546

    Article  PubMed  Google Scholar 

  69. Matte CC et al (2004) Donor APCs are required for maximal GVHD but not for GVL. Nat Med 10(9):987–992

    Article  CAS  PubMed  Google Scholar 

  70. Matzinger P (2002) The danger model: a renewed sense of self. Science 296(5566):301–305

    Article  CAS  PubMed  Google Scholar 

  71. Middleton PG, Taylor PR, Jackson G, Proctor SJ, Dickinson AM (1998) Cytokine gene polymorphisms associating with severe acute graft-versus-host disease in HLA-identical sibling transplants. Blood 92(10):3943–3948

    CAS  PubMed  Google Scholar 

  72. Mielcarek M et al (2003) Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation. Blood 102(2):756–762

    Article  CAS  PubMed  Google Scholar 

  73. Miklos DB et al (2005) Antibody responses to H-Y minor histocompatibility antigens correlate with chronic graft-versus-host disease and disease remission. Blood 105(7):2973–2978

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Miklos DB et al (2004) Antibody response to DBY minor histocompatibility antigen is induced after allogeneic stem cell transplantation and in healthy female donors. Blood 103(1):353–359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Miura Y et al (2004) Association of Foxp3 regulatory gene expression with graft-versus-host disease. Blood 104(7):2187–2193

    Article  CAS  PubMed  Google Scholar 

  76. Miyagawa F, Okiyama N, Villarroel V, Katz SI (2013) Identification of CD3CD4CD8 T Cells as Potential Regulatory Cells in an Experimental Murine Model of Graft-Versus-Host Skin Disease (GVHD). J Invest Dermatol 133:2538–2545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Miyagawa F et al (2008) IL-15 serves as a costimulator in determining the activity of autoreactive CD8 T cells in an experimental mouse model of graft-versus-host-like disease. J Immunol 181(2):1109–1119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Miyagawa F et al (2012) Interferon regulatory factor 8 integrates T-cell receptor and cytokine-signaling pathways and drives effector differentiation of CD8 T cells. Proc Natl Acad Sci U S A 109(30):12123–12128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Mowat AM (1989) Antibodies to IFN-gamma prevent immunologically mediated intestinal damage in murine graft-versus-host reaction. Immunology 68(1):18–23

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Murai M et al (2003) Peyer’s patch is the essential site in initiating murine acute and lethal graft-versus-host reaction. Nat Immunol 4(2):154–160

    Article  CAS  PubMed  Google Scholar 

  81. Nash RA et al (1992) Acute graft-versus-host disease: analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate. Blood 80(7):1838–1845

    CAS  PubMed  Google Scholar 

  82. Nestel FP, Price KS, Seemayer TA, Lapp WS (1992) Macrophage priming and lipopolysaccharide-triggered release of tumor necrosis factor alpha during graft-versus-host disease. J Exp Med 175(2):405–413

    Article  CAS  PubMed  Google Scholar 

  83. Pasquini MC, Wang Z, Horowitz MM, Gale RP (2010) 2010 report from the Center for International Blood and Marrow Transplant Research (CIBMTR): current uses and outcomes of hematopoietic cell transplants for blood and bone marrow disorders. Clin Transpl 87–105

    Google Scholar 

  84. Patriarca F et al (2006) The development of autoantibodies after allogeneic stem cell transplantation is related with chronic graft-vs-host disease and immune recovery. Exp Hematol 34(3):389–396

    Article  CAS  PubMed  Google Scholar 

  85. Pavletic SZ et al (2005) Influence of T-cell depletion on chronic graft-versus-host disease: results of a multicenter randomized trial in unrelated marrow donor transplantation. Blood 106(9):3308–3313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Penack O, Holler E, van den Brink MR (2010) Graft-versus-host disease: regulation by microbe-associated molecules and innate immune receptors. Blood 115(10):1865–1872

    Article  CAS  PubMed  Google Scholar 

  87. Penack O et al (2009) NOD2 regulates hematopoietic cell function during graft-versus-host disease. J Exp Med 206(10):2101–2110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Piguet PF, Grau GE, Allet B, Vassalli P (1987) Tumor necrosis factor/cachectin is an effector of skin and gut lesions of the acute phase of graft-vs.-host disease. J Exp Med 166(5):1280–1289

    Article  CAS  PubMed  Google Scholar 

  89. Przepiorka D et al (1995) 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant 15(6):825–828

    CAS  PubMed  Google Scholar 

  90. Quaranta S et al (1999) Autoantibodies in human chronic graft-versus-host disease after hematopoietic cell transplantation. Clin Immunol 91(1):106–116

    Article  CAS  PubMed  Google Scholar 

  91. Ratanatharathorn V et al (1998) Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation. Blood 92(7):2303–2314

    CAS  PubMed  Google Scholar 

  92. Reddy P et al (2001) Interleukin-18 regulates acute graft-versus-host disease by enhancing Fas-mediated donor T cell apoptosis. J Exp Med 194(10):1433–1440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Sakoda Y et al (2007) Donor-derived thymic-dependent T cells cause chronic graft-versus-host disease. Blood 109(4):1756–1764

    Article  CAS  PubMed  Google Scholar 

  94. Sarantopoulos S et al (2009) Altered B-cell homeostasis and excess BAFF in human chronic graft-versus-host disease. Blood 113(16):3865–3874

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Schaffer JV, McNiff JM, Seropian S, Cooper DL, Bolognia JL (2005) Lichen sclerosus and eosinophilic fasciitis as manifestations of chronic graft-versus-host disease: expanding the sclerodermoid spectrum. J Am Acad Dermatol 53(4):591–601

    Article  PubMed  Google Scholar 

  96. Shimada M et al (2007) Association of autoimmune disease-related gene polymorphisms with chronic graft-versus-host disease. Br J Haematol 139(3):458–463

    CAS  PubMed  Google Scholar 

  97. Shlomchik WD et al (1999) Prevention of graft versus host disease by inactivation of host antigen-presenting cells. Science 285(5426):412–415

    Article  CAS  PubMed  Google Scholar 

  98. Shulman HM et al (2006) Histopathologic diagnosis of chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: II. Pathology Working Group Report. Biol Blood Marrow Transplant 12(1):31–47

    Article  PubMed  Google Scholar 

  99. Sprent J, Schaefer M, Lo D, Korngold R (1986) Properties of purified T cell subsets. II. In vivo responses to class I vs. class II H-2 differences. J Exp Med 163(4):998–1011

    Article  CAS  PubMed  Google Scholar 

  100. Storb R et al (1989) Graft-versus-host disease prevention by methotrexate combined with cyclosporin compared to methotrexate alone in patients given marrow grafts for severe aplastic anaemia: long-term follow-up of a controlled trial. Br J Haematol 72(4):567–572

    Article  CAS  PubMed  Google Scholar 

  101. Svegliati S et al (2007) Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease. Blood 110(1):237–241

    Article  CAS  PubMed  Google Scholar 

  102. Tawara I et al (2008) Combined Th2 cytokine deficiency in donor T cells aggravates experimental acute graft-vs-host disease. Exp Hematol 36(8):988–996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Taylor PA, Lees CJ, Blazar BR (2002) The infusion of ex vivo activated and expanded CD4(+)CD25(+) immune regulatory cells inhibits graft-versus-host disease lethality. Blood 99(10):3493–3499

    Article  CAS  PubMed  Google Scholar 

  104. Teshima T et al (2002) Acute graft-versus-host disease does not require alloantigen expression on host epithelium. Nat Med 8(6):575–581

    Article  CAS  PubMed  Google Scholar 

  105. Toubai T et al (2012) Induction of acute GVHD by sex-mismatched H-Y antigens in the absence of functional radiosensitive host hematopoietic-derived antigen-presenting cells. Blood 119(16):3844–3853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. van Bekkum DW, Roodenburg J, Heidt PJ, van der Waaij D (1974) Mitigation of secondary disease of allogeneic mouse radiation chimeras by modification of the intestinal microflora. J Natl Cancer Inst 52(2):401–404

    PubMed  Google Scholar 

  107. van den Brink MR, Burakoff SJ (2002) Cytolytic pathways in haematopoietic stem-cell transplantation. Nat Rev Immunol 2(4):273–281

    Article  PubMed  CAS  Google Scholar 

  108. Waldman E et al (2006) Absence of beta7 integrin results in less graft-versus-host disease because of decreased homing of alloreactive T cells to intestine. Blood 107(4):1703–1711

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Wang X et al (2011) Mechanisms of antigen presentation to T cells in murine graft-versus-host disease: cross-presentation and the appearance of cross-presentation. Blood 118(24):6426–6437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Weaver J, Bergfeld WF (2010) Quantitative analysis of eosinophils in acute graft-versus-host disease compared with drug hypersensitivity reactions. Am J Dermatopathol 32(1):31–34

    Article  PubMed  Google Scholar 

  111. Weinberg K et al (2001) Factors affecting thymic function after allogeneic hematopoietic stem cell transplantation. Blood 97(5):1458–1466

    Article  CAS  PubMed  Google Scholar 

  112. Williamson E, Garside P, Bradley JA, More IA, Mowat AM (1997) Neutralizing IL-12 during induction of murine acute graft-versus-host disease polarizes the cytokine profile toward a Th2-type alloimmune response and confers long term protection from disease. J Immunol 159(3):1208–1215

    CAS  PubMed  Google Scholar 

  113. Wu H, Brandling-Bennett HA, Harrist TJ (2009) Noninfectous vesiculobullous and vesiculopustular diseases. In: Elder DE (ed) Lever’s histopathology of the skin, 10th edn. Lippincott-Raven, Philadelphia, pp 270–273

    Google Scholar 

  114. Wysocki CA, Panoskaltsis-Mortari A, Blazar BR, Serody JS (2005) Leukocyte migration and graft-versus-host disease. Blood 105(11):4191–4199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Xun CQ, Thompson JS, Jennings CD, Brown SA, Widmer MB (1994) Effect of total body irradiation, busulfan-cyclophosphamide, 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 83(8):2360–2367

    CAS  PubMed  Google Scholar 

  116. Yang YG, Dey BR, Sergio JJ, Pearson DA, Sykes M (1998) Donor-derived interferon gamma is required for inhibition of acute graft-versus-host disease by interleukin 12. J Clin Invest 102(12):2126–2135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Yi T et al (2008) Absence of donor Th17 leads to augmented Th1 differentiation and exacerbated acute graft-versus-host disease. Blood 112(5):2101–2110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Young KJ, DuTemple B, Phillips MJ, Zhang L (2003) Inhibition of graft-versus-host disease by double-negative regulatory T cells. J Immunol 171(1):134–141

    Article  CAS  PubMed  Google Scholar 

  119. Zeiser R et al (2006) Inhibition of CD4+CD25+ regulatory T-cell function by calcineurin-dependent interleukin-2 production. Blood 108(1):390–399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Zeng D et al (1999) Bone marrow NK1.1(−) and NK1.1(+) T cells reciprocally regulate acute graft versus host disease. J Exp Med 189(7):1073–1081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Zhang Y, Louboutin JP, Zhu J, Rivera AJ, Emerson SG (2002) Preterminal host dendritic cells in irradiated mice prime CD8+ T cell-mediated acute graft-versus-host disease. J Clin Invest 109(10):1335–1344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Zhao D et al (2008) In vivo-activated CD103+CD4+ regulatory T cells ameliorate ongoing chronic graft-versus-host disease. Blood 112(5):2129–2138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Zorn E et al (2005) Reduced frequency of FOXP3+ CD4+ CD25+ regulatory T cells in patients with chronic graft-versus-host disease. Blood 106(8):2903–2911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Zorn E et al (2004) Minor histocompatibility antigen DBY elicits a coordinated B and T cell response after allogeneic stem cell transplantation. J Exp Med 199(8):1133–1142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Dermatology, Nara Medical University School of Medicine, 840 Shijo, Kashihara, Nara, 634-8522, Japan

    Fumi Miyagawa M.D., Ph.D.

  2. Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Fumi Miyagawa M.D., Ph.D. & Stephen I. Katz

Authors
  1. Fumi Miyagawa M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephen I. Katz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fumi Miyagawa M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Department of Dermatology, Kyoto University Grad Sch of Med., Sakyo-ku, Kyoto, Japan

    Kenji Kabashima

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Japan

About this chapter

Cite this chapter

Miyagawa, F., Katz, S.I. (2016). Graft Versus Host Disease (GVHD). In: Kabashima, K. (eds) Immunology of the Skin. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55855-2_27

Download citation

Publish with us

Policies and ethics

Search

Navigation