Human Dendritic Cell Expression of HLA-DO Is Subset Specific and Regulated by Maturation1
Journal - The Journal of Immunology
Expression of HLA-DO (DO) in cells that express HLA-DM (DM)results in an altered repertoire of MHC class II/peptide complexes,indicating that DO modulates DM function. Human and murine Bcells and thymic epithelial cells express DO, while monocytes/macrophagesdo not. Monocyte-derived dendritic cells (DC) also have beenfound to be DO-negative, leading to the assumption that DC donot express DO. In this study, we report that, in fact, certaintypes of human primary DC express DO. These include Langerhanscells (LC) and some subtypes of circulating blood DC. Specifically,the majority of BDCA-3+ DC, a small subset of uncertain function,are DO+, while smaller proportions of CD11c+, BDCA-1+ (myeloid)DC, at most a minority of CD123+/BDCA-2+ (plasmacytoid) DC,and no detectable CD16+ (myeloid) DC, express DO. Immunohistochemistryof human tonsil sections demonstrates that tonsillar interdigitatingDC are also DO+. In a subset of immature LC with higher DO expression,an increased fraction of surface DR molecules carry CLIP peptides,indicating that DO functions as a DM inhibitor in these cells.LC expression of DO is down-regulated by maturation stimuli.DM levels also decrease under these conditions, but the DM:DOratio generally increases. In the myeloid cell types tested,DO expression correlates with levels of DO, but not DO, implyingthat modulation of DO regulates DO dimer abundance in thesecells. The range of APC types shown to express DO suggests abroader role for DO in immune function than previously appreciated.