Abstract
Although previous studies have described CD25 expression and production of interleukin-2 (IL-2) by mature dendritic cells (mDCs), it remains unclear how these molecules participate in the activation of T cells. In search of the mechanisms by which daclizumab, a humanized monoclonal antibody against CD25, inhibits brain inflammation in multiple sclerosis, we observed that although the drug has limited effects on polyclonal T cell activation, it potently inhibits activation of antigen-specific T cells by mDCs. We show that mDCs (and antigen-experienced T cells) secrete IL-2 toward the mDC-T cell interface in an antigen-specific manner, and mDCs 'lend' their CD25 to primed T cells in trans to facilitate early high-affinity IL-2 signaling, which is crucial for subsequent T cell expansion and development of antigen-specific effectors. Our data reveal a previously unknown mechanism for the IL-2 receptor system in DC-mediated activation of T cells.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Antibodies, Monoclonal / pharmacology*
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Antibodies, Monoclonal, Humanized
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Antigen Presentation* / drug effects
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Daclizumab
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Dendritic Cells / drug effects
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Dendritic Cells / immunology*
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Humans
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Immunoglobulin G / pharmacology*
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Immunosuppressive Agents / pharmacology
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In Vitro Techniques
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Interleukin-2 / immunology*
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Interleukin-2 Receptor alpha Subunit / antagonists & inhibitors
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Interleukin-2 Receptor beta Subunit / immunology
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Lymphocyte Activation / drug effects
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Models, Immunological
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Multiple Sclerosis / drug therapy
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Multiple Sclerosis / immunology
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Signal Transduction
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology*
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Transplantation Tolerance / drug effects
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Transplantation Tolerance / immunology
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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IL2 protein, human
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IL2RA protein, human
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IL2RB protein, human
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Immunoglobulin G
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Immunosuppressive Agents
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Interleukin-2
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Interleukin-2 Receptor alpha Subunit
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Interleukin-2 Receptor beta Subunit
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Daclizumab