Serotonin Initiation of Delayed-Type Hypersensitivity: Mediation by a Primitive Thy-1⁺ Antigen-Specific Clone or by Specific Monoclonal IgE Antibody

Abstract

Elicitation of delayed-type hypersensitivity (DTH) responses is due to the required sequential action of two different antigen (Ag)-specific Thy-1⁺ cells: early acting, DTH-initiating cells and locally recruited CD4⁺, ΑΒ-TCR⁺, DTH effector T cells. DTH-initiating cells have an unusual phenotype for Ag-specific cells (Thy-1⁺, CD5⁺, CD4^-, CD8^-, CD3^-, slg^-, B220⁺ (CD45RA⁺), Mac 1⁺, IL-2R^- and IL-3R⁺) and act by producing Ag-specific non-IgE factors that sensitize mast cells for release of the vasoactive amine serotonin (5HT) at the local site of elicitation of DTH by challenge. Another mechanism of DTH initiation involves Ag-specific IgE antibodies that also can sensitize mast cells for local serotonin release. Serotonin initiates DTH by activating the local endothelial cells to allow recruitment of DTH effector T cells, and also by activating 5HT-2 receptors on these recruited T cells.

Enteric Neuronal Density Contributes to the Severity of Intestinal Inflammation

“…Nicotinic stimulation (of α7 subunits) is anti-inflammatory 30 and probably accounts for intestinal anti-inflammatory properties of vagus nerve stimulation 31 . Lymphocytes and macrophages also express numerous serotonin receptor subtypes 32 ; moreover, serotonin can initiate DTH 33 , stimulate CD4 cells to secrete IL-16 34 , and promote lymphocyte proliferation 35 . Potentiation of serotonin in serotonin transporter knockout mice increases the severity of colitis induced both by TNBS 36 and by IL-10 deletion 37 .…”

Enteric Neuronal Regulation of Intestinal Inflammation

“…5-HT has been found to modulate chemotaxis, leukocyte activation, proliferation, cytokine secretion, anergy, and apoptosis in immunocytes [82,84]. 5-HT is also vasoactive and plays a role in cell-mediated immunity by facilitating trafficking of lymphocytes through post-capillary venules [85–87]. In addition, 5-HT accumulates in sympathetic nerve terminals in lymphoid tissue and, once in sympathetic terminal axons, enters synaptic vesicles and is co-released along with norepinephrine [88,89].…”

Hyperserotoninemia and Altered Immunity in Autism

“…For instance, DTH and 5-HT play an important role in an animal model of multiple sclerosis, experimental allergic encephalomyelitis (EAE). In EAE, 5-HT initiates the activation of local endothelial cells to recruit DTH effector T cells, and activates 5-HT 2 receptors on these recruited cells (Askenase et al, 1991).…”