Abstract
Histamine is considered one of the important mediators of immediate hypersensitivity and inflammation, and acts via G protein-coupled receptors. Here, we report that histamine may affect antigen receptor-mediated immune responses of T and B cells via a signal(s) from histamine H1 receptors (H1Rs). Histamine exhibited enhancing effects on the in vitro proliferative responses of anti-CD3epsilon- or anti-IgM-stimulated spleen T and B cells, respectively, at the culture condition that the fetal calf serum was dialyzed before culture and c-kit-positive cells were depleted from the spleen cells. In studies of histamine H1R knockout mice, H1R-deficient T cells had low proliferative responses to anti-CD3epsilon cross-linking or antigen stimulation in vitro. B cells from H1R-deficient mice were also affected, demonstrating low proliferative responses to B cell receptor cross-linking. Antibody production against trinitrophenyl-Ficoll was reduced in H1R-deficient mice. Other aspects of T and B cell function were normal in the H1R knockout mice. H1R-deficient T and B cells showed normal responses upon stimulation with interleukin (IL)-2, IL-4, CD40 ligand, CD40 ligand plus IL-4, and lipopolysaccharide. Collectively, these results imply that the signal generated by histamine through H1R augments antigen receptor-mediated immune responses, suggesting cross-talk between G protein-coupled receptors and antigen receptor-mediated signaling.
MeSH terms
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Animals
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Antibodies, Anti-Idiotypic / immunology
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Antibodies, Anti-Idiotypic / pharmacology
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Ascitic Fluid / immunology
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B-Lymphocyte Subsets / immunology*
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Bone Marrow / immunology
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CD3 Complex / immunology
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CD40 Ligand
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Cells, Cultured
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Ficoll / analogs & derivatives
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Ficoll / immunology
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GTP-Binding Proteins / physiology
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Guanosine Triphosphate / metabolism
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Histamine / pharmacology*
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Immunoglobulin M / immunology
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Interleukin-2 / pharmacology
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Interleukin-4 / pharmacology
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Lipopolysaccharides / pharmacology
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Lymphocyte Activation*
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Membrane Glycoproteins / pharmacology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Muromonab-CD3 / immunology
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Muromonab-CD3 / pharmacology
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Ovalbumin / immunology
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Phosphorylation
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Protein Processing, Post-Translational
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Protein-Tyrosine Kinases / metabolism
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Receptors, Antigen, B-Cell / immunology*
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Receptors, Antigen, T-Cell / immunology*
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Receptors, Histamine H1 / deficiency
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Receptors, Histamine H1 / genetics
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Receptors, Histamine H1 / physiology*
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Signal Transduction / physiology*
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Specific Pathogen-Free Organisms
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Spleen / immunology
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T-Lymphocyte Subsets / immunology*
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Thymus Gland / immunology
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Trinitrobenzenes / immunology
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ZAP-70 Protein-Tyrosine Kinase
Substances
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Antibodies, Anti-Idiotypic
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CD3 Complex
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Immunoglobulin M
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Interleukin-2
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Lipopolysaccharides
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Membrane Glycoproteins
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Muromonab-CD3
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Receptors, Antigen, B-Cell
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Receptors, Antigen, T-Cell
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Receptors, Histamine H1
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TNP-ficoll
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Trinitrobenzenes
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anti-IgM
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CD40 Ligand
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Interleukin-4
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Ficoll
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Histamine
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Guanosine Triphosphate
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Ovalbumin
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Protein-Tyrosine Kinases
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ZAP-70 Protein-Tyrosine Kinase
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Zap70 protein, mouse
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GTP-Binding Proteins