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

Abstract

Although numerous reports document a role for CD43 in T cell signaling, the direct participation of this molecule in cell activation has been questioned. In this study we show that CD45 ligation on human normal peripheral T cells was sufficient to induce interleuckin-2, CD69, and CD40-L gene expression, without requiring signals provided by additional receptor molecules. This response was partially inhibited by cyclosporin A and staurosporine, suggesting the participation of both the Ca2+ and the protein kinase C pathways in CD43 signaling. Consistent with the transient CD43-dependent intracellular Ca2+ peaks reported by others, signals generated through the CD43 molecule resulted in the induction of NF-AT DNA binding activity. CD43-dependent signals resulted also in AP-1 and NFκB activation, probably as a result of protein kinase C involvement. AP-1 complexes bound to the AP-1 sequence contained c-Jun, and those bound to the NF-AT-AP-1 composite site contained c-Jun and Fos. NFκB complexes containing p65 could be found as early as 1 h after CD43 cross-linking, suggesting that CD45 participates in early events of T cell activation. The induction of the interleukin-2, CD69, and CD-40L genes and the participation of AP-1, NF-AT, and NFκB in the CD43-mediated signaling cascade implicate an important role for this molecule in the regulation of gene expression and cell function.