Abstract
We investigated the possibility that T helper cells might enhance the stimulatory function of dendritic cells (DCs). We found that ligation of CD40 by CD40L triggers the production of extremely high levels of bioactive IL-12. Other stimuli such as microbial agents, TNF-alpha or LPS are much less effective or not at all. In addition, CD40L is the most potent stimulus in upregulating the expression of ICAM-1, CD80, and CD86 molecules on DCs. These effects of CD40 ligation result in an increased capacity of DCs to trigger proliferative responses and IFN-gamma production by T cells. These findings reveal a new role for CD40-CD40L interaction in regulating DC function and are relevant to design therapeutic strategies using cultured DCs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigen-Presenting Cells / immunology*
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Antigens, CD / metabolism
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B7-1 Antigen / metabolism
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B7-2 Antigen
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CD40 Antigens / physiology*
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CD40 Ligand
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Cell Adhesion
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Cells, Cultured
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Dendritic Cells / immunology*
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Fluorescent Antibody Technique, Indirect
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Histocompatibility Antigens Class II / metabolism
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Humans
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Intercellular Adhesion Molecule-1 / metabolism
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Interferon-gamma / biosynthesis
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Interleukin-12 / biosynthesis*
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Lymphocyte Activation*
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Lymphocyte Cooperation
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Membrane Glycoproteins / metabolism
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Membrane Glycoproteins / physiology
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Signal Transduction
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T-Lymphocytes / immunology*
Substances
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Antigens, CD
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B7-1 Antigen
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B7-2 Antigen
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CD40 Antigens
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CD86 protein, human
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Histocompatibility Antigens Class II
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Membrane Glycoproteins
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Intercellular Adhesion Molecule-1
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CD40 Ligand
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Interleukin-12
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Interferon-gamma