Dendritic cell presentation of antigens from apoptotic cells in a proinflammatory context: Role of opsonizing anti-β2-glycoprotein I antibodies

Patrizia Rovere, Maria Grazia Sabbadini, Cristina Vallinoto, Umberto Fascio, Maria Rescigno, Mariacristina Crosti, Paola Ricciardi-Castagnoli, Genesio Balestrieri, Angela Tincani, Angelo A. Manfredi

Research output: Contribution to journalArticle

Abstract

Objective. To verify whether opsonization of apoptotic cells skews the outcome of apoptotic cell antigen presentation by dendritic cells (DCs). Methods. 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-β2- glycoprotein I antibodies (anti-β2GPI) 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. Results. Anti-β2GPI 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-β2GPI complexed with antigen released from dying cells plays a role in antigen presentation. DCs challenged with low numbers of anti- β2GPI-opsonized apoptotic cells secreted interleukin-1β (IL-1β), tumor necrosis factor α, and IL-10 in an autocrine/paracrine manner. Conclusion. 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.

Original languageEnglish
Pages (from-to)1412-1420
Number of pages9
JournalArthritis and Rheumatism
Volume42
Issue number7
DOIs
Publication statusPublished - Jul 1999

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ASJC Scopus subject areas

  • Immunology
  • Rheumatology

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