CUTANEOUS IMMUNOPATHOLOGY OF CYCLOSPORINE-A-INDUCED AUTOIMMUNITY IN THE RAT

Syngeneic bone marrow transplantation following lethal X-irradiation a nd subsequent administration of cyclosporin A (CsA) results after cess ation of CsA treatment in an autoimmune disease which is thymus depend ent and resembles graft-versus-host disease. The chronic dermal change s of this experimental autoimmune model have similarities with human s cleroderma in terms of skin histopathology. In this study we evaluated the possible role of different effector leukocytes in the rat model o f CsA-induced autoimmunity (CsA-AI) by examining the skin by immunohis tology. In the acute phase both CD4(+) and CD8(+) TCR alpha beta(+) T- cells together with activated ED1(+) macrophages and class II MHC-upre gulated keratinocytes were seen in the epidermis; no selective use of TCR VP was observed. Few TCR alpha beta(+) T-cells were seen in the de rmis where CD4(+) ED2(+) macrophages were abundant. With the change fr om acute to chronic, scleroderma-like lesions the CD4+ T-cells disappe ared from the epidermis and the TCR alpha beta(+) cells were now almos t 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 mechani sm CD4(+) T-cells in the acute-phase of CsA-AI may cause the observed activation of macrophages and keratinocytes. Furthermore, CD4(+) T-cel ls may be necessary for the homing of the CD8(+) T-cells in the epider mis. Especially the activated keratinocytes are suspected of being the target cells which may perpetuate the ongoing autoimmune response int o the chronic phase as established by CD8(+) T-cells only. (C) 1995 Ac ademic Press, Inc.