The thymus and prolonged administration of cyclosporine. Irreversible immunopathologic changes associated with autologous pseudo-graft-versus-host disease

Abstract

Previous studies have demonstrated that short-term administration of cyclosporine leads to immunopathologic changes in the thymus, including medullary involution, loss of Hassall's corpuscles, and decreased class II antigen expression. Generally these changes are rapidly reversible. In rats treated with mediastinal irradiation, however, these changes are irreversible and usually associated with autologous or syngeneic graft-vs.-host disease (pseudo-GVHD). This study describes the immunopathology of the thymus after long-term administration of CsA (7 mg/kg/day, up to 140 days) and monitors the recovery post-CsA. The medulla was markedly involuted at the end of CsA, regardless of duration. The relative size of the medulla showed good recovery. Long-term CsA, however, profoundly delayed or prevented the recovery of Hassall's corpuscles and normal expression of class II antigen. The epithelial cells in Hassall's corpuscles totally disappeared at the end of CsA administration. Following 7 or 28 days of CsA, the Hassall's corpuscles recovered within one month. After 70 days CsA, recovery was delayed until the second month, while after 140 days, Hassall's corpuscles were not present even 2 months post-CsA. Class II antigen was decreased in the subcapsular and juxtamedullary regions at 140 days as well as 1 and 2 months post-CsA. Paralleling the thymic immunopathology, acute and chronic pseudo-GVHD were observed in the skin, tongue, liver, intestines, lacrimal glands, bronchi, and intestines following long-term CsA.