Cyclosporin A and the thymus. Immunopathology.

Cyclosporin A (CsA) is known to diminish the size of the thymus, especially the thymic medulla. The significance of these changes is not presently understood. This study reveals several immunopathologic changes induced in the thymic medulla by CsA (15 mg/kg/day). The weight and relative size of the thymus dramatically and rapidly involutes, with marked changes observed in 1 week. The medullary thymocytes show segregation of rat T-cell phenotypes as seen in control rats, but the number of such cells is markedly reduced in accordance with the medullary remnant. This is consistent with a maturational arrest of thymocytes. The medullary epithelium was assessed directly by irradiating the control or CsA-treated rats 2 days prior to sacrifice. The epithelium of Hassall's corpuscles was essentially absent in CsA-treated rats but prominent in control rats. The cortical epithelial cells were preserved. Stains for Ia antigen with the anti-OX4 antibody show little change in expression by cortical epithelium, but a marked reduction in the Ia+ medullary cells in the thymocyte purged rats. All of these changes were reversible in the normal rat after cessation of CsA, with near normal recovery in 3 weeks. No morphologic or immunopathologic changes were noted in the cortical thymocytes. These cells did, however, acquire CsA receptors, as detected by the binding of fluorescent dansylated CsA.