Dendritic cell presentation of antigens from apoptotic cells in a proinflammatory context: role of opsonizing anti-beta2-glycoprotein I antibodies

To verify whether opsonization of apoptotic cells skews the outcome of apoptotic cell antigen presentation by dendritic cells (DCs). RMA cells, which were engineered with a mutant ovalbumin (OVA) protein and were devoid of the leader secretory sequence (OVA-RMA), underwent ultraviolet irradiation to...

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Bibliographic Details
Published in:	Arthritis and rheumatism Vol. 42; no. 7; pp. 1412 - 1420
Main Authors:	Rovere, P, Sabbadini, M G, Vallinoto, C, Fascio, U, Recigno, M, Crosti, M, Ricciardi-Castagnoli, P, Balestrieri, G, Tincani, A, Manfredi, A A
Format:	Journal Article
Language:	English
Published:	United States 01-07-1999
Subjects:	Antibodies - physiology Antibodies, Antiphospholipid - blood Antigen Presentation Apoptosis - immunology Autoimmunity - physiology beta 2-Glycoprotein I Cell Line Dendritic Cells - immunology Glycoproteins - immunology Histocompatibility Antigens Class II - immunology Humans Interleukin-1 - secretion Interleukin-10 - secretion Microscopy, Confocal Opsonin Proteins - metabolism T-Lymphocytes - immunology Tumor Cells, Cultured
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Summary:	To verify whether opsonization of apoptotic cells skews the outcome of apoptotic cell antigen presentation by dendritic cells (DCs). RMA cells, which were engineered with a mutant ovalbumin (OVA) protein and were devoid of the leader secretory sequence (OVA-RMA), underwent ultraviolet irradiation to induce apoptosis. Binding of anti-beta2-glycoprotein I antibodies (anti-beta2GPI) and phagocytosis of apoptotic cells were assessed by flow cytometry and confocal microscopy. Presentation of processing antigens and major histocompatibility complex (MHC) class II-restricted or MHC class I-restricted antigens was assessed using OVA-specific T cell hybridomas. Anti-beta2GPI facilitated presentation of epitopes from internalized apoptotic cells to MHC class II-restricted, but not to class I-restricted, T lymphocytes. DCs challenged with supernatants of apoptotic cells did not activate OVA-specific T cells, making it unlikely that anti-beta2GPI complexed with antigen released from dying cells plays a role in antigen presentation. DCs challenged with low numbers of anti-beta2GPI-opsonized apoptotic cells secreted interleukin-1beta (IL-1beta), tumor necrosis factor alpha, and IL-10 in an autocrine/paracrine manner. Opsonization influences the outcome of the disposal of low numbers of apoptotic cells by DCs. This implies that soluble factors bound to apoptotic cells modulate their immunogenicity.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0004-3591