HLA-DR-mediated apoptosis susceptibility discriminates differentiation stages of dendritic/monocytic APC

Professional APC are characterized by their ability to present peptide via HLA class II in the presence of costimulatory molecules (CD40, CD80, and CD 86), The efficiency of Ag presentation can be classed as follows: mature de ndritic cells (DC) are most efficient, immature DC and macrophages are inte rmediate, and monocytes are considered poor APC, There is a large body of e vidence demonstrating that HLA-DR transmits signals in the APC, In this stu dy, we have addressed the question of the outcome of HLA-DR signals on APC of the monocyte/DC lineages throughout their differentiation from immature to mature APC, DC were generated from both monocytes and CD34(+) cells of t he same individual, macrophages were differentiated from monocytes, Immunop henotypical analysis clearly distinguished these populations. HLA-DR-mediat ed signals led to marked apoptosis in mature DC of either CD34 or monocytic origin. Significantly less apoptosis was observed in immature DC of either origin, Nonetheless, even immature DC were more susceptible to HLA-DR-medi ated apoptosis than macrophages, whereas monocytes were resistant to HLA-DR -mediated apoptosis, The mechanism of HLA-DR-mediated apoptosis was indepen dent of caspase activation. Taken together, these data lead to the notion t hat signals generated via HLA-DR lead to the demise of mature professional APC, thereby providing a means of limiting the immune response.