IL-1 beta enhances CD40 ligand-mediated cytokine secretion by human dendritic cells (DC): A mechanism for T cell-independent DC activation

CD40 ligand (CD40L) is a membrane-bound molecule expressed by activated T cells. CD40L potently induces dendritic cell (DC) maturation and IL-12p70 secretion and plays a critical role during T cell priming in the lymph nodes. IFN-γ and IL-4 are required for CD40L-mediated cytokine secretion, suggesting that T cells are required for optimal CD40L activity. Because CD40L is rapidly up-regulated by non-T cells during inflammation, CD40 stimulation may also be important at the primary infection site. However, a role for T cells at the earliest stages of infection is unclear. The present study demonstrates that the innate immune cell-derived cytokine, IL-1β, can increase CD40L-induced cytokine secretion by monocyte-derived DC, CD34-derived DC, and peripheral blood DC independently of T cell-derived cytokines. Furthermore, IL-1β is constitutively produced by monocyte-derived DC and monocytes, and is increased in response to intact Escherichia coli or CD40L, whereas neither CD34-derived DC nor peripheral blood DC produce IL-1β. Finally, DC activated with CD40L and IL-1β induce higher levels of IFN-γ secretion by T cells compared with DC activated with CD40L alone. Therefore, IL-1β is the first non-T cell-derived cytokine identified that enhances CD40L-mediated activation of DC. The synergy between CD40L and IL-1β highlights a potent, T cell-independent mechanism for DC activation during the earliest stages of inflammatory responses