CD7 expression and galectin-1-induced apoptosis of immature thymocytes are directly regulated by NF-kappaB upon T-cell activation.

ABSTRACT

CD7, one of the galectin-1 receptors, has crucial roles in galectin-1-mediated apoptosis of activated T-cells and T-lymphoma progression in peripheral tissues. In this study, we showed that CD7 promoter activity was increased by NF-kappaB and that this activity was synergistic when Sp1 was co-expressed in the immature T-cell line L7. Site-directed mutagenesis analysis of the CD7 promoter indicated that NF-kappaB specifically bound to the NF-kappaE2 site in cooperation with Sp1. Overexpression of E12 or Twist2 proteins negatively regulated NF-kappaB-mediated activity of the CD7 proximal promoter. In addition, CD7 expression was down-regulated by treatment with the p38 MAPK inhibitor SB20358, or the MSK1 inhibitor H-89. These signaling pathway inhibitors prevented galectin-1-mediated apoptosis of immature T-cells. From these results, we concluded that the regulation of CD7 gene expression through NF-kappaB activation induced by TCR/CD28 might have significant implications for T-cell homeostasis.