Thymus atrophy in the nonhuman primate by FK506: An immunohistochemical study

Abstract

F K 506 is a potent anti-lymphocytic and immunosuppressive agent with a totally distinct structure from the cyclic peptide cyclosporin A (CyA), but with the same selective, inhibitory action on CD4+ lymphocyte activation and cytokine gene expression.‘” FIG06 suppresses both humoral and cell-mediated immunity and is highly effective in prolonging organ allograft survival in a variety of species, including rodents, non-human primates, and man at considerably lower doses than CyA.6-“’ Concerning the adverse effects of immunosuppressive drugs on the thymus, the capacity of CyA to alter the thymic microenvironment in normal or allografted animals is well characterized.” There is evidence that the drug interferes with thymocyte differentiation and maturation both in viva” and in vitro.‘“,‘4 The effects of FKS06 on the thymus have been studied in rats and mice. Thymic medullary atrophy has been demonstrated after short term exposure (6 to 14 days) to the drug.“-*’ There are substantial interspecies differences with regard to the effects of FK.506.831” The discrepant findings concerning the immunosuppressive potency and toxicity of the drug in non-human primates indicated the need for further non-human primate studies. 20-22 Therefore, we investigated the immunotoxic effects of FK506 on the thymic environment and T lymphocyte development in young adult Cynomolgus monkeys.