title: Altered dendritic cells with tolerizing phenotype in patients with systemic lupus erythematosus.
abstract: Earlier we showed the generation of tolerizing human monocyte-derived DC following interaction with iC3b-opsonized apoptotic cells. In this study we examine the generation of DC with our previously described tolerogenic phenotype in patients with the systemic autoimmune disease systemic lupus erythematosus (SLE). Monocyte-derived DC were generated in 71 SLE patients, characterized, and then tested for clearance of iC3b-opsonized 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanineperchlorate-stained apoptotic cells using flow cytometry, and for autologous T-cell activation using autologous mixed lymphocyte reaction (AMLR), at the same time as controls. Compared with healthy, age- and gender-matched controls, SLE patients showed upregulation of MHC class II, with a mean expression of 130.5%+/-36.8% (p < 0.007); CD86 in immature DC from SLE patients, generated in autologous human or control plasma, were also upregulated, with mean expression 106.6%+/-18.0% (p < 0.03). A significant (> 20%) reduction in iC3b-apoptotic cell uptake, together with increased autologous mixed lymphocyte reaction, was seen in 75% of SLE patients. Mean 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanineperchlorate-stained apoptotic cell acquisition was 70.0%+/-24% (p < 0.0001) compared with healthy controls. Altered generation of a tolerizing DC phenotype was seen in at least one third of SLE patients following interaction with iC3b-opsonized apoptotic cells. These results suggest that a substantial portion of SLE patients fail to generate DC with a tolerizing phenotype.
authors.affiliation: The Laboratory for Cellular and Molecular Immunology, Rheumatology Unit, Department of Medicine, Hadassah-Hebrew University, Jerusalem, Israel.
authors.forename: Yackov
authors.initials: Y
authors.lastname: Berkun
authors.forename: Inna
authors.initials: I
authors.lastname: Verbovetski
authors.forename: Anat
authors.initials: A
authors.lastname: Ben-Ami
authors.forename: Daphna
authors.initials: D
authors.lastname: Paran
authors.forename: Dan
authors.initials: D
authors.lastname: Caspi
authors.forename: Alon
authors.initials: A
authors.lastname: Krispin
authors.forename: Uriel
authors.initials: U
authors.lastname: Trahtemberg
authors.forename: Oranit
authors.initials: O
authors.lastname: Gill
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Naparstek
authors.forename: Dror
authors.initials: D
authors.lastname: Mevorach
mesh_terms: D017209:Apoptosis; D051940:B7-2 Antigen / Q000276:immunology / Q000378:metabolism*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D009895:Opsonin Proteins / Q000276:immunology; D010587:Phagocytosis; D017634:Self Tolerance
chemical_list: D051940:B7-2 Antigen; D000949:Histocompatibility Antigens Class II; D009895:Opsonin Proteins