Abstract
Antigen-specific suppression of a previously primed immune response is a major challenge for immunotherapy of autoimmune disease. RelB activation is required for myeloid DC differentiation. Here, we show that antigen-exposed DCs in which RelB function is inhibited lack cell surface CD40, prevent priming of immunity, and suppress previously primed immune responses. DCs generated from CD40-deficient mice similarly confer suppression. Regulatory CD4+ T cells induced by the DCs transfer antigen-specific "infectious" tolerance to primed recipients in an interleukin-10-dependent fashion. Thus CD40, regulated by RelB activity, determines the consequences of antigen presentation by myeloid DCs. These observations have significance for autoimmune immunotherapy and suggest a mechanism by which peripheral tolerance might be constitutively maintained by RelB(-) CD40(-) DCs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens
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Autoimmune Diseases / therapy
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CD4-Positive T-Lymphocytes / immunology*
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CD40 Antigens / metabolism
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Hemocyanins
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Immune Tolerance
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Immunotherapy
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Interferon-gamma / biosynthesis
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Interleukin-10 / biosynthesis*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Ovalbumin / immunology
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Proto-Oncogene Proteins / deficiency
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / immunology
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Transcription Factor RelB
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Transcription Factors / deficiency
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Transcription Factors / genetics
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Transcription Factors / immunology
Substances
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Antigens
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CD40 Antigens
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Proto-Oncogene Proteins
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Relb protein, mouse
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Transcription Factors
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Interleukin-10
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Transcription Factor RelB
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Interferon-gamma
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Ovalbumin
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Hemocyanins
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keyhole-limpet hemocyanin