Triggering HLA-DR molecules on human peripheral monocytes induces their death

Although engagement of MHC class II molecules on human monocytes triggers v arious cellular events, their possible role in monocyte death is yet unknow n. We demonstrate that ligation of MHC class II on primary monocytes induce s a rapid cell death that has all the characteristics of monocyte apoptosis , does not require de novo protein synthesis, is independent from both Fas and TNF-alpha systems, and is not rescued by ligation of CD40. However, cel l-cell interactions that involve the beta 2-integrin CD18 seem to be critic al for the execution of this monocyte death. Priming monocytes with IFN-gam ma enhances significantly their HLA-DR-mediated death whereas LPS treatment effectively reverses this death process. Thus, our results describe the MH C class II molecules, in particular HLA-DR, as mediators of monocyte death and suggest that this novel pathway of monocyte death might have an importa nt role in controlling the outcome of inflammatory process and the regulati on of monocyte hemostasis. (C) 1999 Academic Press.