Triggering HLA-DR Molecules on Human Peripheral Monocytes Induces Their Death

Although engagement of MHC class II molecules on human monocytes triggers various cellular events, their possible role in monocyte death is yet unknown. We demonstrate that ligation of MHC class II on primary monocytes induces a rapid cell death that has all the characteristics of monocyte apoptosis, does not requirede novoprotein synthesis, is independent from both Fas and TNF-α systems, and is not rescued by ligation of CD40. However, cell–cell interactions that involve the β2-integrin CD18 seem to be critical for the execution of this monocyte death. Priming monocytes with IFN-γ enhances significantly their HLA-DR-mediated death whereas LPS treatment effectively reverses this death process. Thus, our results describe the MHC class II molecules, in particular HLA-DR, as mediators of monocyte death and suggest that this novel pathway of monocyte death might have an important role in controlling the outcome of inflammatory process and the regulation of monocyte hemostasis.