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The Journal of Immunology, Vol 143, Issue 10 3134-3140, Copyright © 1989 by American Association of Immunologists

ARTICLES

Effect of cyclosporin A on lymphopoiesis. II. Developmental defects of immature and mature thymocytes in fetal thymus organ cultures treated with cyclosporin A

A Kosugi, JC Zuniga-Pflucker, SO Sharrow, AM Kruisbeek and GM Shearer
Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892.

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.


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