T-cell activation triggers death receptor-6 expression in a NF-κB and NF-AT dependent manner

Abstract

Death receptor-6 (DR6) apparently participates in the regulation of T-cell activation and/or activity as its genetic disruption results in enhanced CD4+ T-cell expansion, the production of Th2 cytokines, and interestingly also the compromised migration of CD4+ T cells to sites of inflammation. However, the mechanism of regulation of DR6 expression in cells of the immune system is not fully understood. In this communication we show that DR6 is not expressed in resting T cells from human peripheral blood or murine lymph nodes but that its expression is significantly upregulated in CD3 crosslinking- or PMA/ionomycin-activated T lymphocytes. DR6 expression is transiently increased in both activated human CD4+ and CD8+ T cells and it is apparently dependent on the activation of NF-κB and NF-AT signaling pathways. In contrast to primary peripheral blood T cells, the widely used model lymphoblastic leukemia T-cell line Jurkat is DR6-positive and unexpectedly, TCR-mediated stimulation of Jurkat cells strongly downregulates DR6 expression via suppression of its transcription.