International Immunology, Vol. 11, No. 8, 1203-1216,
August 1999
© 1999 Japanese Society for Immunology
A dominant-negative mutant of c-Jun inhibits cell cycle progression during the transition of CD4–CD8– to CD4+CD8+ thymocytes
Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda MD 20892, USA
1 Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA
2 Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Correspondence to: L. B. King, University of Pennsylvania School of Medicine, Room 535 CRB, 415 Curie Boulevard, Philadelphia, PA 19104, USA
While Jun/Fos-containing transcription factors are known to be necessary for many TCR-mediated events in mature T cells, relatively little is known about their roles in thymocyte development. We have generated transgenic mice that express a trans-dominant-negative mutant of c-Jun (TAM-67) specifically in thymocytes. Expression of TAM-67 inhibited the up-regulation of AP-1-responsive genes such as c-jun and IL-2 in stimulated thymocytes from transgenic mice. In addition, altered thymocyte development in TAM-67-expressing mice was revealed by a decrease in thymic cellularity (~50%) which could be accounted for primarily by a reduction in the number of CD4+CD8+ thymocytes, a large percentage of which retained CD25. The decrease in the number of CD4+CD8+ thymocytes did not appear to be due to an enhanced rate of apoptosis but rather to a decrease in the number of CD4–CD8–CD25– cells in the S + G2/M stages of the cell cycle. These results indicate that Jun/Fos-containing transcription factors promote the proliferative burst that accompanies the transition from the CD4–CD8– to the CD4+CD8+ stage of thymocyte development.
Keywords: cellular differentiation, thymus, transcription factor, transgenic/knockout
Transmitting editor: D. R. Littman
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