THE LESIONS OF CYCLOSPORINE-INDUCED AUTOIMMUNE-DISEASE CAN BE EQUALLYWELL ELICITED BY CD4 OR CD8 EFFECTOR T-CELLS

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.