A dominant-negative mutant of c-Jun inhibits cell cycle progression during the transition of CD4-CD8- to CD4+CD8+ thymocytes

Leslie B. King, Eva Tolosa, Joi M. Lenczowski, Frank Lu, Evan F. Lind, Rosemarie Hunziker, Howard T. Petrie, Jonathan D. Ashwell

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1203-1215
Number of pages13
JournalInternational Immunology
Volume11
Issue number8
DOIs
StatePublished - 1999

Keywords

  • Cellular differentiation
  • Thymus
  • Transcription factor
  • Transgenic/knockout

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    King, L. B., Tolosa, E., Lenczowski, J. M., Lu, F., Lind, E. F., Hunziker, R., Petrie, H. T., & Ashwell, J. D. (1999). A dominant-negative mutant of c-Jun inhibits cell cycle progression during the transition of CD4-CD8- to CD4+CD8+ thymocytes. International Immunology, 11(8), 1203-1215. https://doi.org/10.1093/intimm/11.8.1203