CD4 T cells activated in the mesenteric lymph node mediate gastrointestinal food allergy in mice

Abstract

A localized Th2 milieu has been observed in the intestine of subjects with food allergic disorders; however, the role of T cells in the pathophysiology of these disorders remains poorly understood. Our aim was to examine sites of T cell activation in response to food challenge, identify potential factors responsible for T cell recruitment to the gut, and determine the role of T cells in disease. BALB/c mice were systemically sensitized to ovalbumin (OVA) and repeatedly fed with OVA to induce allergic diarrhea. Local cytokine and chemokine expressions were assessed by quantitative PCR, and cytokine secretion levels in the mesenteric lymph node (MLN) were determined by ELISA. Homing molecule expression was determined by flow cytometry, and the role of CD4(+) T cells in promoting disease was tested by adoptive transfer. Mice developed diarrhea associated with changes in epithelial ion transport, mast cell infiltration, intestinal IgE secretion, and local upregulation of Th2 cytokines and the Th2 chemokines CCL1, CCL17, and CCL22 in the small intestine. T cell activation occurred in the MLN before symptom onset, and a single feed of OVA induced T cell proliferation, alpha(4)beta(7) upregulation, and CD62L downregulation. Cells from the MLN, including purified CD4(+) T cells, were able to transfer allergic diarrhea to naive mice. A gut-homing phenotype induced in the MLN and selective upregulation of Th2 chemoattractants are likely important factors in the gastrointestinal recruitment of pathological Th2-skewed CD4(+) T cells in food allergy.

Gastrointestinal Immune Response to the Shrimp Allergen Tropomyosin: Histological and Immunological Analysis in an Animal Model of Shrimp Tropomyosin Hypersensitivity

“…Eosinophils constitute another principal effector cell type that induces gastrointestinal tissue injury and disease pathogenesis through the release of various toxic granule proteins, lipid mediators and proinflammatory cytokines [34] . Compared with other allergy models, the accumulation of inflammatory cells in these mice does not require repetitive intragastric challenge [15,35] . The gastrointestinal tract mucus layer is the front line of innate host defense [36] .…”

“…Wang et al [16] reported a 20% incidence of diarrhea after one challenge. Moreover, Knight et al [35] reported an incidence of 100% after a single dose challenge in their OVA murine model, while lower allergen doses reduced the incidence.…”

Eosinophilic Disorders in Various Diseases

“…Food allergies have been noted in 13-25% with specific positive IgE due to certain foods in 40% of adults [27,28]. These allergies are thought to be mediated by activated CD4 + T cells, found in the mesenteric lymph nodes [29].…”

Chemokine receptors in allergic diseases

“…Moreover, the allergic response is characterized by Th2 proliferation, and Th2-associated cytokines and chemokines can be found in the serum of allergic patients. In a model of food allergy in mice, the receptor CCR8 and the ligands of CCR4, CCL17, and CCL22 were overexpressed in the intestine (70). Once again, the receptor CX3CR1 is also involved in food allergies.…”