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.
In this report, we investigate the effect of cyclosporin A (CsA) on lymphopoiesis, and demonstrate that CsA selectively 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.
Kosugi
A
A
Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892.
Sharrow
S O
SO
Shearer
G M
GM
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte; D001402:B-Lymphocytes / Q000187:drug effects / Q000502:physiology; D001853:Bone Marrow / Q000187:drug effects; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000187:drug effects; D003524:Cyclosporins / Q000008:administration & dosage*; D006410:Hematopoiesis / Q000187:drug effects*; D007958:Leukocyte Count / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000145:classification / Q000187:drug effects; D051379:Mice; D010641:Phenotype; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000145:classification / Q000187:drug effects* / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects*
D000945:Antigens, Differentiation, T-Lymphocyte; D003524:Cyclosporins