TY - JOUR
T1 - Dendritic cell presentation of antigens from apoptotic cells in a proinflammatory context
T2 - Role of opsonizing anti-β2-glycoprotein I antibodies
AU - Rovere, Patrizia
AU - Sabbadini, Maria Grazia
AU - Vallinoto, Cristina
AU - Fascio, Umberto
AU - Rescigno, Maria
AU - Crosti, Mariacristina
AU - Ricciardi-Castagnoli, Paola
AU - Balestrieri, Genesio
AU - Tincani, Angela
AU - Manfredi, Angelo A.
PY - 1999/7
Y1 - 1999/7
N2 - 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.
AB - 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.
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U2 - 10.1002/1529-0131(199907)42:7<1412::AID-ANR15>3.0.CO;2-T
DO - 10.1002/1529-0131(199907)42:7<1412::AID-ANR15>3.0.CO;2-T
M3 - Article
C2 - 10403269
AN - SCOPUS:0033496383
VL - 42
SP - 1412
EP - 1420
JO - Arthritis care and research : the official journal of the Arthritis Health Professions Association
JF - Arthritis care and research : the official journal of the Arthritis Health Professions Association
SN - 0893-7524
IS - 7
ER -