Abstract
Interactions with self-major histocompatibility complex molecules on dendritic cells (DCs) are important for the survival of mature CD4+ T cells. We have followed the DC-mediated signal from the T cell surface to the nucleus and identified a pattern of activation that correlates with increased in vitro survival. This response is induced exclusively by DCs and is likely associated with a modulation of the T cell activation threshold. We have also found that DC-mediated activation results in antigen-independent cytokine gene expression, which points to a new role for DCs in shaping the cytokine milieu. Such antigen-independent activation of T cells may play a role in protective immunity, but may also induce and perpetuate autoimmune states such as multiple sclerosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens / immunology
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Antigens, Differentiation, T-Lymphocyte / metabolism
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Cell Differentiation
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Cell Survival
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Cells, Cultured
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Clone Cells
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Dendritic Cells / cytology
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Dendritic Cells / immunology*
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Humans
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Interferon-gamma / biosynthesis
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Interferon-gamma / genetics
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Lymphocyte Activation*
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Protein-Tyrosine Kinases / metabolism
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RNA, Messenger / biosynthesis
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Receptors, Antigen, T-Cell / metabolism
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Receptors, Interleukin / biosynthesis
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Receptors, Interleukin / genetics
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Receptors, Interleukin-12
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Signal Transduction*
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology*
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ZAP-70 Protein-Tyrosine Kinase
Substances
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Antigens
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Antigens, Differentiation, T-Lymphocyte
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RNA, Messenger
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Receptors, Antigen, T-Cell
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Receptors, Interleukin
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Receptors, Interleukin-12
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Interferon-gamma
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Protein-Tyrosine Kinases
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ZAP-70 Protein-Tyrosine Kinase
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ZAP70 protein, human