Jgmc. Damoiseaux et al., CUTANEOUS IMMUNOPATHOLOGY OF CYCLOSPORINE-A-INDUCED AUTOIMMUNITY IN THE RAT, Clinical immunology and immunopathology, 77(3), 1995, pp. 315-323
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.