CD43-mediated signals induce DNA binding activity of AP-1, NF-AT, and NF kappa B transcription factors in human T lymphocytes

Although numerous reports document a role for CD43 in T cell signaling, the direct participation of this molecule in cell activation has been question ed. In this study we show that CD43 ligation on human normal peripheral T c ells was sufficient to induce interleukin-2, CD69, and CD40-L gene expressi on, without requiring signals provided by additional receptor molecules. Th is response was partially inhibited by cyclosporin A and staurosporine, sug gesting the participation of both the Ca2+ and the protein kinase C pathway s in CD43 signaling. Consistent with the transient CD43-dependent intracell ular Ca2+ peaks reported by others, signals generated through the CD43 mole cule resulted in the induction of NF-AT DNA binding activity. CD43-dependen t signals resulted also in AP-1 and NF kappa B activation, probably as a re sult of protein kinase C involvement. AP-1 complexes bound to the AP-1 sequ ence contained c-Jun, and those bound to the NF-AT-AP-1 composite site cont ained c-Jun and Fos. NF kappa B complexes containing p65 could be found as early as 1 h after CD43 crosslinking, suggesting that CD43 participates in early events of T cell activation. The induction of the interleukin-a, CD69 , and CD-40L genes and the participation of AP-1, NF-AT, and NF kappa B in the CD43-mediated signaling cascade implicate an important role for this mo lecule in the regulation of gene expression and cell function.