Effects of cyclosporin A on mouse thymus: immunochemical and ultrastructural studies.

Abstract

The in vivo effect of cyclosporin A (CsA) on the murine thymus was investigated by studying the ultrastructural cellular alterations, which are described for the first time, and the immunohistochemical modifications of thymocytes and thymic reticulo-epithelial cells (TREC). A marked reduction of the thymus size became apparent after 6 days of CsA treatment (10 mg/kg/day). Light microscopy studies using polyclonal antibodies (Ab) or monoclonal Ab specific to lymphoid sub-populations (anti-CD4, anti-CD5, anti-CD8), and specific to epithelial cells (anti-keratin: AKs, K8), to cortical TREC (TR4) and to subcapsular/medullary TREC (TR5, 3H9) showed that the number of CD4- 8+ or CD4+ 8- medullary thymocytes dramatically decreased and that the cortical TREC are affected, after 10 days of CsA treatment. These observations were confirmed by electron microscopy studies demonstrated that the medullary lymphoid population disappeared almost entirely. TREC, principally cortical type, presented signs of cellular lysis. A few cortical thymocytes showed some damage. At day 8 the medullary thymic tissue was disorganized, but no change was noted in the subcapsular area right up to the final day (day 10) of CsA treatment. These results suggest that CsA has a harmful effect on cortical TREC, which affects the development of immature thymocytes.