Overcoming food allergy through acquired tolerance conferred by transfer of Tregs in a murine model

Abstract

We concluded that oral tolerance for food antigens is induced in two ways: (i) by initial exposure to antigen, or inherent tolerance, and (ii) by transfer of Tregs, or acquired tolerance. Because food allergies occur when inherent tolerance is absent, understanding of acquired tolerance is important for the development of therapies for food allergy.

Low-Dose IL-2 Induces Regulatory T Cell–Mediated Control of Experimental Food Allergy

“…In addition, transfer of Tregs inhibited and reversed airway hyperresponsiveness, gut inflammation, and related Th2 responses in murine models (13)(14)(15). Collectively, these data highlight that allergic diseases result from an inappropriate balance between allergen-activated effector Th2 cells and Tregs, and that treatments to enhance Treg responses might be useful in prevention and treatment of allergic diseases.…”

“…However, specific Treg-based immunotherapies have not been evaluated in the context of food allergy. For this purpose, we established an experimental model based on previous work (15), comprising sensitization with OVA/alum i.p. injections followed by administration of high amounts of OVA by repeated intragastric delivery.…”

“…Based on published procedures (15) with specific modifications, BALB/c mice were sensitized twice at 1-wk interval by i.p. injection of 10 mg OVA (Ova A5503; Sigma-Aldrich) mixed with 500 mg aluminum hydroxide (Alum) gel (AlH 3 O 3 ; Sigma) or PBS mixed with Alum as control (nonsensitized mice [NS]).…”

Histamine-releasing factor enhances food allergy

“…The development of diarrhea was monitored for 90 minutes after OVA challenge. Diarrhea severity (30) was based on states of stool: solid (score 0), funicular (score 1), slurry (score 2), and watery (score 3).…”

Novel insights into mechanisms of food allergy and allergic airway inflammation using experimental mouse models

“…Induction of tolerance correlated with expansion of Foxp3 + CD4 + T cells and depletion of Treg resulted in impaired oral tolerance (14). Similarly, Yamashita and colleagues provided evidence that adoptive transfer of mesenteric lymph nodes (or Treg) isolated from mice orally pretreated with OVA prevented recipient mice from anaphylactic responses (15).…”