Enhanced CD4+ T Cell Proliferation and Th2 Cytokine Production in DR6-Deficient Mice

AbstractWe have found that DR6, a member of the TNF receptor family, is highly expressed in resting T cells and downregulated in activated T cells. DR6-targeted mutant mice were generated and showed normal development. However, DR6−/− CD4+ T cells hyperproliferated in response to TCR-mediated stimulation and protein antigen challenge. Activated DR6−/− CD4+ T cells exhibited upregulated CD25 expression and enhanced proliferation in response to exogenous IL-2 stimulation. In addition, increased CD28 and reduced CTLA-4 expression were observed in these cells. Enhanced Th2 cytokine production by activated DR6−/− CD4+ T cells was associated with the increased transcription factor NF-ATc in nuclei. DR6, therefore, functions as a regulatory receptor for mediating CD4+ T cell activation and maintaining proper immune responses