T-cell maturation and clonal deletion in cyclosporine-induced autoimmunity

In some circumstances cyclosporine (CyA) induces autoimmune phenomena, and a lethal form of syngeneic graft-vs-host disease (SGVHD) can be induced in rats by the administration of CyA. Although several rat strains develop this disease, in this study, we report that of six mouse strains tested, only the DBA/2 strain developed SGVHD. A comparison of the effect of CyA on thymocytic and peripheral T-cell populations revealed that CyA-induced alterations were similar in the two species, although more marked in rats. Notably, CyA-treated syngeneic bone marrow chimeras (SBMC) had transiently increased numbers of peripheral CD4+ CD8+ T-cells, expressing a marker normally limited to thymocytes. Examination of T-cell receptor (TCR) V beta expression in CyA-treated mice revealed a normal pattern of clonal deletion in all strains (including disease-prone DBA/2 mice), suggesting that CyA may induce autoimmunity without blocking intrathymic clonal deletion.