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


RESULTS
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.


CONCLUSIONS
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.
Istituto Scientifico H.S. Raffaele, and University of Milan, Italy.
P
P
Rovere
M G
MG
Sabbadini
C
C
Vallinoto
U
U
Fascio
M
M
Recigno
M
M
Crosti
P
P
Ricciardi-Castagnoli
G
G
Balestrieri
A
A
Tincani
A A
AA
Manfredi
D000906:Antibodies / Q000502:physiology; D017152:Antibodies, Antiphospholipid / Q000097:blood; D017951:Antigen Presentation; D017209:Apoptosis / Q000276:immunology*; D015551:Autoimmunity / Q000502:physiology; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018613:Microscopy, Confocal; D009895:Opsonin Proteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured; D053482:beta 2-Glycoprotein I
D000906:Antibodies; D017152:Antibodies, Antiphospholipid; D006023:Glycoproteins; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D009895:Opsonin Proteins; D053482:beta 2-Glycoprotein I; D016753:Interleukin-10