Immunosuppression with cyclosporin A alters the thymic microenvironment

The effect of cyclosporin A (CyA) immunosuppression on the murine thymic microenvironment and T lymphocyte development has been analysed using monoclonal antibodies to epithelial and lymphocyte subpopulations, macrophages and major histocompatibility complex (MHC) class II antigens in immunohistochemistry and flow cytometry. The major microenvironmental target for CyA-induced damage was the thymic medulla, where a reduction in all epithelial cell subsets, dendritic cells and macrophages was observed. In contrast, the thymic cortex appeared essentially normal. CyA had no detectable effect on the intensity of microenvironmental expression of MHC class II molecules in either cortex or medulla, although the number of MHC class II positive medullary cells was reduced after CyA treatment. CyA also had a differential effect on the thymic lymphocyte populations where there was little change in the Thy-1 bright, CD5 dull, CD4+, CD8+ cortical thymocytes but a depletion of the Thy-1 dull, CD5 bright, CD4 or CD8 single-positive medullary cells. This lymphocyte loss may be due partly to increased migration from thymus to spleen and other peripheral lymphoid organs, and partly to a block in the differentiation stage from cortical to medullary lymphocyte. The thymic microenvironment and lymphocyte subpopulations recover rapidly after cessation of CyA treatment, although there may be longer term functional defects resulting from the CyA-induced injury.