CYCLOSPORINE-A-INDUCED CHANGES OF THE THYMIC MICROENVIRONMENT - A REVIEW OF MORPHOLOGICAL-STUDIES

Cyclosporin A is an immunosuppressive drug, which disrupts the activat ion of peripheral T-lymphocyte pool and blocks the maturation of thymo cytes within the thymus. Normally, thymic nonlymphoid cells provide th e optimal inductive microenvironment for development of T-lymphocytes. After application of cyclosporin A the complex alterations of the thy mic microenvironment occur, affecting all types of nonlymphoid cells. All subsets of thymic epithelial cells are thoroughly changed. The sub capsular epithelial cells show the prominent enlargement of cytokerati n contents. In electron microscopy, however, these cells present the m orpho-functional aspect of resting cells. The epithelial cells in deep er cortex become enlarged and stockier, whereby their cell processes a ppear more ramified and thicker. Thus, the cytoreticulum they create s eems much denser. These cells strongly express MHC antigens. Their sub cellular organization is suggestive of increased synthetic and secreto ry activity. The number of medullary epithelial cells is decreased. Th e cells with the most mature phenotype are the most prominently deplet ed and the ones with phenotypically and morphologically immature appea rance predominate. The number of Hassall's bodies is also decreased. T he number of cortical macrophages does not increase. However, these ce lls become enlarged showing the prominent changes in enzyme capacity, histochemical features and ultrastructural organization. Thus, they be come similar to macrophages located in the cortico-medullary zone of t he normal rat thymus. Cortical macrophages increase the activity of hy drolytic enzymes, acid phosphatase and nonspecific esterase, develop t he strong activity of chloroacetate esterase, the strong activity of r espiratory enzyme succinic dehydrogenase and begin to show the marked presence of prostaglandin synthase. Moreover, the cytoplasmic inclusio ns, which are aldehyde fuchsin- and PAS-positive and show sudanophilia , appear within cortical macrophages. In electron microscopy these cel ls show an abundant cytoplasm a very active appearance and the variety of vacuolar cytoplasmic inclusions. The mitoses of neighboring thymoc ytes are often seen. The number of interdigitating cells is decreased due to reduced size of thymic medulla, but these cells do not show the substantial phenotypic changes. The description and classification of all types of nonlymphoid cells, which constitute the normal thymic mi croenvironment, is also presented. The functional significance and pos sible mechanisms of CSA-induced changes of the thymic microenvironment are discussed.