       Document 0718
 DOCN  M9620718
 TI    Cutaneous immunopathology of cyclosporin-A-induced autoimmunity in the
       rat.
 DT    9602
 AU    Damoiseaux JG; Beijleveld LJ; van Breda Vriesman PJ; Department of
       Immunology, University of Limburg, Maastricht, The; Netherlands.
 SO    Clin Immunol Immunopathol. 1995 Dec;77(3):315-23. Unique Identifier :
       AIDSLINE MED/96080360
 AB    Syngeneic bone marrow transplantation following lethal X-irradiation and
       subsequent administration of cyclosporin A (CsA) results after cessation
       of CsA treatment in an autoimmune disease which is thymus dependent and
       resembles graft-versus-host disease. The chronic dermal changes of this
       experimental autoimmune model have similarities with human scleroderma
       in terms of skin histopathology. In this study we evaluated the possible
       role of different effector leukocytes in the rat model of CsA-induced
       autoimmunity (CsA-AI) by examining the skin by immunohistology. In the
       acute phase both CD4+ and CD8+ TCR alpha beta + T-cells together with
       activated ED1+ macrophages and class II MHC-upregulated keratinocytes
       were seen in the epidermis; no selective use of TCR V beta was observed.
       Few TCR alpha beta + T-cells were seen in the dermis where CD4+ ED2+
       macrophages were abundant. With the change from acute to chronic,
       scleroderma-like lesions the CD4+ T-cells disappeared from the epidermis
       and the TCR alpha beta + cells were now almost exclusively CD8+; both
       class II MHC-upregulated keratinocytes and macrophages persisted.
       Changes in TCR gamma delta + T-cells were not observed in the acute or
       chronic phase. As a possible effector mechanism CD4+ T-cells in the
       acute-phase of CsA-AI may cause the observed activation of macrophages
       and keratinocytes. Furthermore, CD4+ T-cells may be necessary for the
       homing of the CD8+ T-cells in the epidermis. Especially the activated
       keratinocytes are suspected of being the target cells which may
       perpetuate the ongoing autoimmune response into the chronic phase as
       established by CD8+ T-cells only.
 DE    Animal  Antibodies, Monoclonal/IMMUNOLOGY  Autoimmune
       Diseases/*CHEMICALLY INDUCED/PATHOLOGY  Bone Marrow Transplantation
       Cyclosporine/*TOXICITY  CD4-Positive T-Lymphocytes/IMMUNOLOGY
       CD8-Positive T-Lymphocytes/IMMUNOLOGY  Female  Histocompatibility
       Antigens Class II/IMMUNOLOGY  Immunoenzyme Techniques
       Macrophages/IMMUNOLOGY  Rats  Rats, Inbred Lew  Receptors, Antigen,
       T-Cell, alpha-beta/IMMUNOLOGY  Receptors, Antigen, T-Cell,
       gamma-delta/IMMUNOLOGY  Skin/IMMUNOLOGY/*PATHOLOGY  Skin
       Diseases/IMMUNOLOGY/*PATHOLOGY  Specific Pathogen-Free Organisms
       Support, Non-U.S. Gov't  Thymectomy  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

