Cutaneous immunopathology of cyclosporin-A-induced autoimmunity in the rat.
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.
Damoiseaux
J G
JG
Department of Immunology, University of Limburg, Maastricht, The Netherlands.
Beijleveld
L J
LJ
van Breda Vriesman
P J
PJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000473:pathology; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016572:Cyclosporine / Q000633:toxicity*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007124:Immunoenzyme Techniques; D008264:Macrophages / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology*; D012871:Skin Diseases / Q000276:immunology / Q000473:pathology*; D013047:Specific Pathogen-Free Organisms; D013934:Thymectomy
D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016572:Cyclosporine