Effect of cyclosporin A on lymphopoiesis. II. Developmental defects of immature and mature thymocytes in fetal thymus organ cultures treated with cyclosporin A.
The effect of cyclosporin A (CsA) on early T cell development was studied by two-color flow cytometric and biochemical analyses using the fetal thymus organ culture system. Addition of CsA to organ culture resulted in a decreased cell yield and complete inhibition of the appearance of TCR-alpha beta-bearing, single positive thymocytes (both CD4+CD8- and CD4-CD8+). Furthermore, the generation of CD4+CD8+ thymocytes was markedly inhibited by CsA treatment, whereas the development of CD3-, CD4-CD8+ thymocytes and TCR-gamma delta-bearing, CD4-CD8- thymocytes was not affected. These results suggest that CsA induces a maturational arrest of T cells entirely within the thymic environment, and indicate that CsA-induced inhibition occurs at more than one stage of intrathymic T cell development.
Kosugi
A
A
Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892.
Zuniga-Pflucker
J C
JC
Sharrow
S O
SO
Kruisbeek
A M
AM
Shearer
G M
GM
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D003524:Cyclosporins / Q000494:pharmacology*; D005333:Fetus; D006131:Growth Inhibitors / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D011948:Receptors, Antigen, T-Cell / Q000032:analysis / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology / Q000502:physiology*
D003524:Cyclosporins; D006131:Growth Inhibitors; D011948:Receptors, Antigen, T-Cell