Granzyme-B-Containing Lymphocyte Involvement in Epidermal Injury in Graft-versus-Host Disease

Background: Skin lesions from graft-versus-host disease (GVHD) show histological features of epidermal cell death with lymphocyte infiltration. Perforin and granzyme B are involved in the process of apoptosis induced by cytotoxic T lymphocytes (CTL). Objective: To elucidate the role of CTL in the mechanism of epidermal injury in GVHD. Methods: We studied immunohistochemical staining for granzyme B and perforin in the skin lesions of 8 patients who developed GVHD after bone marrow transplantation. Results: Granzyme-B-positive lymphocytes were CD8 positive and were observed in the epidermis of 3 out of 6 specimens in acute GVHD, and of 5 specimens of chronic GVHD except for 1 sclerotic type in which it was negative. Perforin-positive lymphocytes were observed in the epidermis of the specimens from 1 acute and 1 chronic GVHD. Conclusions: Granzyme B derived from CTL may be involved in the mechanisms of epidermal injury in GVHD.

[1]  K. Oshimi,et al.  Differential Effects of Anti-Fas Ligand and Anti-Tumor Necrosis Factor α Antibodies on Acute Graft-Versus-Host Disease Pathologies , 1998 .

[2]  F. Bauters,et al.  Involvement of TNF-alpha secreting macrophages in lethal forms of human graft-versus-host disease , 1997, Bone Marrow Transplantation.

[3]  T. Ley,et al.  Perforin/granzyme-dependent and independent mechanisms are both important for the development of graft-versus-host disease after murine bone marrow transplantation. , 1997, The Journal of clinical investigation.

[4]  M. Kawashima,et al.  The role of granzyme B-expressing CD8-positive T cells in apoptosis of keratinocytes in lichen planus , 1997, Archives of Dermatological Research.

[5]  R. Langley,et al.  Apoptosis is the mode of keratinocyte death in cutaneous graft-versus-host disease. , 1996, Journal of the American Academy of Dermatology.

[6]  T. Ley,et al.  The role of granzyme B in murine models of acute graft-versus-host disease and graft rejection. , 1996, Blood.

[7]  R. Zinkernagel,et al.  Molecular mechanisms of lymphocyte-mediated cytotoxicity and their role in immunological protection and pathogenesis in vivo. , 1996, Annual review of immunology.

[8]  E D Thomas,et al.  1994 Consensus Conference on Acute GVHD Grading. , 1995, Bone marrow transplantation.

[9]  M. Takata Immunohistochemical identification of perforin-positive cytotoxic lymphocytes in graft-versus-host disease. , 1995, American journal of clinical pathology.

[10]  F. Carnot,et al.  Perforin and granzyme B expression is associated with severe acute rejection. Evidence for in situ localization in alveolar lymphocytes of lung-transplanted patients. , 1994, Transplantation.

[11]  N. Vallée,et al.  Granzyme B and perforin can be used as predictive markers of acute rejection in heart transplantation , 1994, European journal of immunology.

[12]  A. Hess,et al.  Graft-versus-host disease: new directions for a persistent problem. , 1994, Blood.

[13]  J. Saurat,et al.  The lichen planus like and sclerotic phases of the graft versus host disease in man: an ultrastructural study of six cases. , 1981, Acta dermato-venereologica.

[14]  J. Kerr,et al.  Apoptosis: Its nature and implications for dermatopathology , 1979, The American Journal of dermatopathology.

[15]  J. Saurat,et al.  Lichen-planus-like eruption following bone marrow transplantation: a manifestation of the graft-versus-host disease. , 1977, Clinical and experimental dermatology.

[16]  G. Achten,et al.  Graft versus host reaction. An ultrastructural study. , 1975, Archives of dermatology.

[17]  R. Storb,et al.  Histopathology of graft-vs.-host reaction (GvHR) in human recipients of marrow from HL-A-matched sibling donors. , 1974, Transplantation proceedings.