Ly6C(low) monocytes differentiate into dendritic cells and cross-tolerize T cells through PDL-1.
Monocyte-derived dendritic cells are active participants during the immune response against infection, but whether they play a role in maintaining self-tolerance under steady-state conditions is not known. Here we investigated the differentiation of monocytes, their ability to ingest apoptotic cells, and their potential functionality in vivo. We observed that Ly6C (Gr-1)(low) mature monocytes up-regulate their MHC II level in the spleen, express high levels of PDL-1 (programmed death ligand 1), and are more efficient than Ly6C(high) immature monocytes in the ingestion of apoptotic cells in vivo. Sorted circulating Ly6C(low) monocytes were able to cross-present both apoptotic cell-associated OVA and soluble OVA protein. Monocytes containing apoptotic cells can further differentiate into CD11c(+)CD8alpha(-)MHC II(+) splenic dendritic cells that maintained high expression of PDL-1. Since wild-type but not PDL-1-deficient peripheral blood monocytes containing apoptotic cell-associated OVA suppressed the response to OVA immunization, PDL-1 expression was required for monocyte-mediated T cell tolerance. These observations demonstrate that Ly6C(low) mature monocytes can promote tolerance to self Ag contained in apoptotic cells through a PDL-1-dependent mechanism.
Peng
YuFeng
Y
Division of Rheumatology, University of Washington, Seattle, WA 98195, USA.
Latchman
Yvette
Y
Elkon
Keith B
KB
D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis*; D017209:Apoptosis / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000502:physiology*; D060890:B7-H1 Antigen; D002454:Cell Differentiation / Q000276:immunology*; D045142:Cross-Priming / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D007108:Immune Tolerance; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology; D010455:Peptides / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation
D000950:Antigens, Ly; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; C494192:Ly-6C antigen, mouse; D008562:Membrane Glycoproteins; D010455:Peptides; D010047:Ovalbumin