Ljj. Beijleveld et al., THE LESIONS OF CYCLOSPORINE-INDUCED AUTOIMMUNE-DISEASE CAN BE EQUALLYWELL ELICITED BY CD4 OR CD8 EFFECTOR T-CELLS, Transplantation, 62(10), 1996, pp. 1468-1476
Lethally irradiated Lewis rats reconstituted with syngeneic bone marro
w and given cyclosporine for 4 weeks develop a graft-versus-host-like
disease upon withdrawal of CsA, Autoreactive T cells inducing this thy
mus-dependent autoimmune disease, termed CsA-AI, are demonstrable by a
doptive transfer, provided regulatory cells in recipient rats are elim
inated. Earlier studies have not unequivocally defined the effector T
cells responsible for development of CsA-AI, Some of these studies sug
gest that both CD4 and CD8 T cells are required, while other studies i
ndicate disease transfer by CD4 or CD8 T cells only, To further clarif
y this issue, it was necessary to study putative effector T cells in a
well-defined setting, Hence, adoptive transfer studies were designed
wherein the effect of the T cells of interest could be studied without
being influenced by T cells of unwanted origin, Accordingly, recipien
t rats were thymectomized prior to irradiation, lymph node cells (LNC)
from diseased donor rats were depleted of CD4 or CD8 cells before ado
ptive transfer, and recipients were treated in vivo with CD4- or CD8-d
epleting mAb, The results showed that CsA-AI developed after adoptive
transfer with LNC depleted of either CD4 or CD8 cells, Analysis of PBL
and of histologic specimens confirmed the absence of the depleted sub
set, In both instances, the typical MHC class II expression on keratin
ocytes and the presence of ED1+ macrophages were identical to the lesi
ons in the primary donors, where both CD4 and CDS T cells were present
, Analysis of the T cell Receptor beta-chain variable region repertoir
es revealed that their expression patterns in LNC of diseased donors o
r recipients was comparable to that in normal thymus or LNC-hence, the
re was no restricted BV repertoire, Taken in toto, our observations in
dicate that CsA-AI involves both CD4 and CD8 T cells, and that these s
ubsets can generate identical macroscopic and microscopic signs of dis
ease.