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

While Jun/Fos-containing transcription factors are known to be necessary fo r many TCR-mediated events in mature T cells, relatively little is known ab out their roles in thymocyte development. We have generated transgenic mice that express a trans-dominant-negative mutant of c-Jun (TAM-67) specifical ly 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 trans genic mice. In addition, altered thymocyte development in TAM-67-expressing mice was revealed by a decrease in thymic cellularity (similar to 50%) whi ch could be accounted for primarily by a reduction in the number of CD4(+)C D8(+) thymocytes, a large percentage of which retained CD25, The decrease i n the number of CD4(+)CD8(+) thymocytes did not appear to be due to an enha nced 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 i ndicate that Jun/Fos-containing transcription factors promote the prolifera tive burst that accompanies the transition from the CD4(-)CD8(-) to the CD4 (+)CD8(+) stage of thymocyte development.