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

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.