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

Academic Article
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Overview

authors

  • King, L. B.
  • Tolosa, E.
  • Lenczowski, J. M.
  • Lu, F.
  • Lind, E. F.
  • Hunziker, R.
  • Petrie, Howard
  • Ashwell, J. D.

publication date

  • August 1999

journal

  • International Immunology  Journal

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 ( approximately 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 + G(2)/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.

subject areas

  • Animals
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Cell Cycle
  • Cell Differentiation
  • Gene Expression Regulation, Developmental
  • Genes, jun
  • Interleukin-2
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Knockout
  • Mice, Transgenic
  • Proto-Oncogene Proteins c-jun
  • Receptors, Interleukin-2
  • T-Lymphocyte Subsets
  • Thymus Gland
  • Transcription Factor AP-1
  • Transcription Factors
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Research

keywords

  • cellular differentiation
  • thymus
  • transcription factor
  • transgenic/knockout
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Identity

International Standard Serial Number (ISSN)

  • 0953-8178

Digital Object Identifier (DOI)

  • 10.1093/intimm/11.8.1203

PubMed ID

  • 10421778
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Additional Document Info

start page

  • 1203

end page

  • 1215

volume

  • 11

issue

  • 8

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