Differential induction of IL-1β and tumor necrosis factor by CD40 ligand or cellular contact with stimulated T cells depends on the degree of maturity of human monocytes

Excerpt

Cellular contact with stimulated T cells potently induces cytokine production in monocytes, a mechanism likely to be of relevance to chronic inflammation. Although the identity of the surface molecules involved in this process remains elusive, CD40 and its ligand CD40L are thought to be implicated, considering that they are expressed at the inflammatory site. To assess the involvement of CD40L we compared the activation of three different types of human monocytic cells: freshly isolated monocytes, monocytes primed with interferon gamma (IFNγ-macrophages), and THP-1 cells. These cells were activated by either membranes isolated from stimulated T cells (HUT-78 or T lymphocytes) to mimic cellular contact, by soluble extracts from isolated membranes, or by CD40L trimer (CD40LT). The production of tumor necrosis factor (TNF) and IL-1β was induced by membranes of stimulated T cells in the three types of target cells, whereas CD40LT induced TNF production in IFNγ-macrophages only. Similar results were obtained with soluble extracts of T-cell membranes, demonstrating that the difference between membranes and CD40LT was not due to the particulate form of membranes. CD40LT induced neither transcript nor protein of cytokines in monocytes, whereas in IFNγ-macrophages IL-1β and TNF mRNA were observed, only TNF being detected in cell supernatants. Finally, anti-CD40L antibodies failed to inhibit TNF and IL-1β production induced in IFNγ-macrophages by solubilized membranes, while TNF production induced by CD40LT was inhibited. These results demonstrate that CD40L is not required in monocyte activation by direct cellular contact with stimulated T cells, although soluble CD40LT induces the production of TNF in IFNγ-macrophages. …