C-REL REGULATION OF IL-2 GENE-EXPRESSION MAY BE MEDIATED THROUGH ACTIVATION OF AP-1

T cell activation by antigen/MHC induces the expression of several gen es critical to the immune response, including interleukin-2. T cells f rom mice deficient for the NF-kappa B family member c-rel cannot activ ate IL-2 gene expression. However, mutating the NF-kappa B site in the IL-2 promoter has only moderate effects. To investigate additional wa ys c-Rel could regulate IL-2 gene expression, we determined whether c- rel overexpression could increase the activity of other transcription factors involved in IL-2 promoter regulation: NF-AT, Oct/OAP (ARRE-1), and AP-1. In Jurkat TAg cells, overexpression of c-Rel increased AP-1 activation similar to 17-fold. Moreover, AP-1 activity stimulated, by anti-TCR Abs or PMA/ionomycin was further increased by c-Rel overexpr ession. c-Rel overexpression did not affect NF-AT or ARRE-1 activity. Additionally, overexpression of c-Rel activated the nonconsensus AP-1 site from the IL-2 promoter (NF-IL-2B), although to a lesser extent, a pproximately sixfold. AP-1 activation required both the DNA binding an d transactivation domains of c-Rel. Our results may provide an explana tion for the effect on IL-2 gene activation in c-rel-deficient mice.