HLA-DR-Mediated Apoptosis Susceptibility Discriminates Differentiation Stages of Dendritic/Monocytic APC

• Published in: The Journal of immunology (1950) 2000-03, Vol.164 (5), p.2379-2385
• Main Authors: Bertho, Nicolas, Drenou, Bernard, Laupeze, Beatrice, Berre, Claudine Le, Amiot, Laurence, Grosset, Jean-Marc, Fardel, Olivier, Charron, Dominique, Mooney, Nuala, Fauchet, Renee
• Format: Article
• Language: English
• Subjects: Antigen-Presenting Cells - cytology; Antigen-Presenting Cells - enzymology; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; Antigens, CD34 - biosynthesis; Apoptosis - drug effects; Apoptosis - immunology; Caspase Inhibitors; CD34 antigen; Cell Differentiation - drug effects; Cell Differentiation - immunology; Cell Line; Dendritic Cells - cytology; Dendritic Cells - enzymology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dose-Response Relationship, Immunologic; Enzyme Inhibitors - pharmacology; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - immunology; Hematopoietic Stem Cells - metabolism; histocompatibility antigen HLA; HLA-DR Antigens - immunology; Humans; Immunity, Innate - drug effects; Immunophenotyping; Life Sciences; Macrophages - cytology; Macrophages - immunology; Monocytes - cytology; Monocytes - immunology; Monocytes - metabolism; Tumor Cells, Cultured
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.164.5.2379

Professional APC are characterized by their ability to present peptide via HLA class II in the presence of costimulatory molecules (CD40, CD80, and CD86). The efficiency of Ag presentation can be classed as follows: mature dendritic cells (DC) are most efficient, immature DC and macrophages are intermediate, and monocytes are considered poor APC. There is a large body of evidence demonstrating that HLA-DR transmits signals in the APC. In this study, 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 the same individual, macrophages were differentiated from monocytes. Immunophenotypical analysis clearly distinguished these populations. HLA-DR-mediated 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-mediated apoptosis than macrophages, whereas monocytes were resistant to HLA-DR-mediated apoptosis. The mechanism of HLA-DR-mediated apoptosis was independent of caspase activation. Taken together, these data lead to the notion that signals generated via HLA-DR lead to the demise of mature professional APC, thereby providing a means of limiting the immune response.