Immunologic characterization of 3 murine regimens of allergen-specific immunotherapy
Open accessAbstract
Background Allergen-specific immunotherapy (ASIT) is used to treat the symptoms of immediate type I hypersensitivity. The mechanisms driving establishment of allergen tolerance are not yet fully understood.Objective The goal of this study was to develop and immunologically characterize 3 murine models of ASIT to simulate protocols currently used to treat patients with type I hypersensitivities.Methods Ovalbumin (OVA)-sensitized mice were desensitized to OVA by means of repeated injections of OVA with a rapid, intermediate, or gradual protocol. After desensitization, mice were assessed for clinical sensitivity to OVA, and immunologic parameters were assessed.Results Mice in all treatment protocols displayed decreased vascular permeability in response to OVA challenge after desensitization. Circulating OVA-specific IgE levels, as well as basophil activation in response to OVA stimulation and IgE cross-linking, were significantly decreased in all treatment groups. Intermediate and gradual protocols, but not rapid desensitization, suppressed splenocyte proliferation and production of IL-4, IL-5, and IFN-γ in response to OVA and polyclonal activation. Similarly, significant increases in IL-10 production, numbers of CD4(+)CD25(+) forkhead box protein 3-positive regulatory T cells, and OVA-specific IgG1 antibody levels were only observed in mice undergoing prolonged ASIT regimens.Conclusion Suppression of IgE-mediated activation is a common feature of all desensitization schedules. Induction of immunoregulatory networks requires prolonged desensitization schedules.
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Treg cells play a major role in allergen tolerance and allergen immunotherapy.
“Treg cells play a major role in allergen tolerance and allergen immunotherapy (AIT).371-373”
From International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (2018) · cites this paper as [372]
The Discussion says Treg-associated regulatory mechanisms may be important for allergen tolerance in the intermediate and gradual murine immunotherapy regimens. The results report increased Treg numbers in those regimens, but not in the rapid regimen; the paper also cautions that Treg responses do not always correlate with clinical benefit. It therefore supports a possible role, not the unqualified claim that Treg cells play a major role in allergen tolerance and AIT generally. (LLM, conf=0.87)
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References 49 · Cited by 15
Research works printed but not linked: 1
- Francis JN, Till SJ, Durham SR. Induction of IL-101CD41CD251 T cells by grass pollen immunotherapy. J Allergy Clin Immunol 2003;111:1255-61.
- Authors
- Fox, E. M., Torrero, M. N., Evans, H., & Mitre, E.
- Affiliations
- Uniformed Services University of the Health Sciences (US)
- Corresponding author
- Mitre, Edward
- ORCID
- Mitre, Edward
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 135
- Issue
- 5
- Pages
- 1341-1351.e7
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W2119696572
- Cited by
- 15
- References
- 49
- Citations by year
- 2023: 1 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 5 · 2015: 2
- FWCI
- 2.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Allergic Rhinitis and Sensitization
- Health Sciences › Medicine › Immunology and Allergy › Food Allergy and Anaphylaxis Research
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Keywords
- allergen immunotherapy, allergen desensitization, immediate hypersensitivity, ovalbumin sensitization, IgE-mediated activation, basophil activation, regulatory T cells, IL-10, Th1/Th2 cytokines, splenocyte proliferation, vascular permeability, allergen tolerance, murine allergy model
- MeSH terms
- Allergens, Anaphylaxis, Animals, Basophils, Desensitization, Immunologic, Disease Models, Animal, Female, Hypersensitivity, Immediate, Immunoglobulin Isotypes, Ovalbumin, Spleen, T-Lymphocyte Subsets, Cytokines, T-Lymphocytes, Regulatory, Mice, Immunomodulation
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