Low-Dose Allergen-Specific Immunotherapy Induces Tolerance in a Murine Model of Shrimp Allergy

Int Arch Allergy Immunol. 2017;174(2):86-96. doi: 10.1159/000479694. Epub 2017 Oct 25.


Background: The efficacy and safety of allergen-specific immunotherapy (AIT) are highly dose-dependent.

Methods: We investigated the dosage effects of AIT and the underlying mechanisms in a murine model of shrimp hypersensitivity. BALB/c mice were sensitized with recombinant shrimp allergen rMet e 1 and challenged orally with a high dose of rMet e 1 to elicit an allergic response. These sensitized mice were then treated with a low (0.01 mg), medium (0.05 mg), or high dosage (0.1 mg) of rMet e 1 intraperitoneally before receiving a second oral challenge. The allergic responses and immunological changes in the gut were compared between animals receiving different dosages.

Results: We found that all sensitized mice that received rMet e 1 immunotherapy were desensitized, regardless of the dosage, and protected at the second oral challenge. Nevertheless, the mice in the high-dosage group experienced severe systemic reactions during the treatment phase. In contrast, regulatory T (Treg) cell-associated genes were upregulated only in the low- and medium-dosage groups, and Foxp3+ cells were more abundant in the gut lymphoid tissues than in the high-dosage group.

Conclusions: Our results demonstrate that low-dosage immunotherapy favors the induction of local Foxp3+ Treg cells and the upregulation of regulatory cytokines. The safety advantages and long-term efficacy of low-dosage immunotherapy should be taken into consideration when developing immunotherapy dose schedules.

Keywords: Desensitization; Dosage; Foxp3; Regulatory T cells; Tropomyosin.

MeSH terms

  • Allergens / immunology*
  • Allergens / therapeutic use*
  • Anaphylaxis / immunology
  • Anaphylaxis / pathology
  • Animals
  • Antibodies / blood
  • Cytokines / biosynthesis
  • Desensitization, Immunologic / methods*
  • Disease Models, Animal
  • Food Hypersensitivity / immunology
  • Food Hypersensitivity / therapy*
  • Immune Tolerance / immunology
  • Immunoglobulin E / blood
  • Immunoglobulin G / blood
  • Intestine, Small / immunology
  • Intestine, Small / pathology
  • Mice
  • Mice, Inbred BALB C
  • Penaeidae / immunology
  • Proteins / immunology*
  • T-Lymphocytes, Regulatory / immunology*


  • Allergens
  • Antibodies
  • Cytokines
  • Immunoglobulin G
  • Met e 1 allergen
  • Proteins
  • Immunoglobulin E