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 Lind, Rosemarie Hunziker, Howard T. Petrie, Jonathan D. Ashwell

Research output: Contribution to journalArticle

13 Citations (Scopus)

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
Externally publishedYes

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Thymocytes
Cell Cycle
Transgenic Mice
Transcription Factors
Transcription Factor AP-1
Interleukin-2
Up-Regulation
Apoptosis
T-Lymphocytes
Genes

Keywords

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

ASJC Scopus subject areas

  • Immunology

Cite this

A dominant-negative mutant of c-Jun inhibits cell cycle progression during the transition of CD4-CD8- to CD4+CD8+ thymocytes. / King, Leslie B.; Tolosa, Eva; Lenczowski, Joi M.; Lu, Frank; Lind, Evan; Hunziker, Rosemarie; Petrie, Howard T.; Ashwell, Jonathan D.

In: International Immunology, Vol. 11, No. 8, 1999, p. 1203-1215.

Research output: Contribution to journalArticle

King, LB, Tolosa, E, Lenczowski, JM, Lu, F, Lind, E, Hunziker, R, Petrie, HT & Ashwell, JD 1999, 'A dominant-negative mutant of c-Jun inhibits cell cycle progression during the transition of CD4-CD8- to CD4+CD8+ thymocytes', International Immunology, vol. 11, no. 8, pp. 1203-1215. https://doi.org/10.1093/intimm/11.8.1203
King, Leslie B. ; Tolosa, Eva ; Lenczowski, Joi M. ; Lu, Frank ; Lind, Evan ; Hunziker, Rosemarie ; Petrie, Howard T. ; Ashwell, Jonathan D. / A dominant-negative mutant of c-Jun inhibits cell cycle progression during the transition of CD4-CD8- to CD4+CD8+ thymocytes. In: International Immunology. 1999 ; Vol. 11, No. 8. pp. 1203-1215.
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