Abstract
To investigate whether the increased rate of lymphocyte apoptosis in systemic lupus erythematosus is involved in the onset of the disease, apoptotic or necrotic T or B lymphocytes from various cell lines were injected intraperitoneally into pre-autoimmune (NZBxNZW)F1 mice (BW) and non-autoimmune BALB/c mice. The intraperitoneal production of cytokines and chemokines, the specific T cell response in the spleen, and the production of anti-histone and anti-dsDNA Ab were investigated. The onset of the disease was characterized by creatinine levels and evaluation of glomerular IgG deposits. In BW, but not in BALB/c mice, injection of apoptotic and not necrotic cells up-regulated IL-6 and IL-10 in resident macrophages. Administration of apoptotic cells augmented the number of Th2 and B lymphocytes recruited in the peritoneal cavity. Only the treatment with apoptotic B cells promoted a systemic Th2 autoimmune response to H2 histones, associated with earlier occurrence of high levels of anti-dsDNA autoantibodies, higher creatinine levels and more numerous glomerular IgG deposits than in BW controls not injected with apoptotic B cells. In genetically susceptible mice exposure to apoptotic of B, but not T, lymphocytes can elicit a Th2 response to H2 histones that helps B cell production of anti-dsDNA Ab and finally triggers the onset of lupus.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Antinuclear / analysis
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Antibodies, Antinuclear / immunology
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Apoptosis*
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Autoantibodies / analysis
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Autoantibodies / immunology
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Autoantigens / immunology*
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Autoimmune Diseases / blood
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Autoimmune Diseases / immunology*
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Autoimmune Diseases / pathology
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B-Lymphocytes / pathology*
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Chemokines / biosynthesis
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Creatinine / blood
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DNA / immunology
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Disease Models, Animal
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Disease Progression
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Epitopes, T-Lymphocyte / immunology
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Female
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Histones / classification
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Histones / immunology*
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Immunization
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Immunoglobulin G / analysis
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Immunoglobulin G / immunology
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Interferon-gamma / biosynthesis
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Interferon-gamma / blood
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Interleukin-4 / biosynthesis
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Interleukin-4 / blood
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Kidney Glomerulus / chemistry
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Kidney Glomerulus / immunology
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Kidney Glomerulus / pathology
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Leukemia, T-Cell / immunology
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Leukemia, T-Cell / pathology
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Lupus Erythematosus, Systemic / blood
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Lupus Erythematosus, Systemic / immunology*
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Lupus Erythematosus, Systemic / pathology
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Lupus Nephritis / blood
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Lupus Nephritis / immunology
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Lupus Nephritis / pathology
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Lymphocyte Cooperation
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Mice
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Mice, Inbred BALB C
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Mice, Inbred NZB
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Phagocytosis
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Plasmacytoma / immunology
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Plasmacytoma / pathology
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Spleen / immunology
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T-Lymphocyte Subsets / immunology
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Th2 Cells / immunology
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Tumor Cells, Cultured
Substances
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Antibodies, Antinuclear
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Autoantibodies
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Autoantigens
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Chemokines
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Epitopes, T-Lymphocyte
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Histones
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Immunoglobulin G
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Interleukin-4
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Interferon-gamma
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DNA
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Creatinine