Effect of cyclosporin A on lymphopoiesis. I. Absence of mature T cells in thymus and periphery of bone marrow transplanted mice treated with cyclosporin A
Kosugi, A.; Sharrow, S.O.; Shearer, G.M.
Journal of Immunology 142(9): 3026-3032
1989
ISSN/ISBN: 0022-1767 PMID: 2651520 Document Number: 328018
In this report, we investigate the effect of cyclosporin A (CsA) on lymphopoiesis, and demonstrate that CsA selectivity abrogates the development of CD4+CD8- and CD4-CD8+ T cells (single positive cells) in the thymus. This developmental arrest results in the complete absence of mature T cells (assessed both by phenotypic and functional analyses) in the spleen of syngeneic bone marrow transplanted mice subsequently treated with CsA. In contrast to its remarkable effect on T cells, CsA had no detectable effect on B cells differentiation. In the thymus, the generation of CD4+CD8+ thymocytes was not affected by CsA treatment, and CD4-CD8- thymocytes of CsA-treated mice expressed surface markers characteristic of normal CD4-CD8- thymocytes, and exhibited normal functional activity when stimulated with anti-CD3 antibody. Thus, CsA appears to prevent the generation of mature, single positive T cells without affecting the development of immature T cells in the thymus. In addition to its immunosuppressive effect on immunocompetent cells, these results indicate a novel feature of CsA, which involves arrest of T cell differentiation, a finding that may be important for applications in clinical bone marrow transplantation.