Evaluating the in vivo Th2 priming potential among common allergens

Exposure to allergens, both man-made and from our environment is increasingly associated with the development of significant human health issues such as allergy and asthma. Allergen induced production of the cytokine interleukin (IL-)4 by Th2 cells is central to the pathogenesis of allergic disease...

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Bibliographic Details
Published in:Journal of immunological methods 2013-08, Vol.394 (1-2), p.62-72
Main Authors: Camberis, Mali, Prout, Melanie, Tang, Shiau-Choot, Forbes-Blom, Elizabeth, Robinson, Marcus, Kyle, Ryan, Belkaid, Yasmine, Paul, William, Le Gros, Graham
Format: Article
Language:English
Subjects:
Allergenicity
Allergens - immunology
Animals
CD4 T cell
CD4-Positive T-Lymphocytes - immunology
eGFP-reporter
Female
House dust mite
Humans
In vivo Th2 immunoassay
Interleukin-4
Lipopolysaccharides - pharmacology
Male
Mice
Mice, Inbred C57BL
Skin - immunology
Th2 Cells - immunology
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Summary:Exposure to allergens, both man-made and from our environment is increasingly associated with the development of significant human health issues such as allergy and asthma. Allergen induced production of the cytokine interleukin (IL-)4 by Th2 cells is central to the pathogenesis of allergic disease (Gavett et al., 1994). The development of the G4 mouse, that expresses green fluorescent protein (GFP) as a surrogate for IL-4 protein expression has made it possible to directly track the immune cells that produce IL-4. By combining a reliable intradermal immunisation technique with the transgenic G4 mouse we have been able to develop a novel & unique in vivo primary Th2 immune response model (PTh2). When allergens relevant to human disease are evaluated using the PTh2 assay a dose dependent hierarchy of allergenicity is revealed with environmental allergens (cockroach, house dust mite) the most potent and food allergens being the least. In addition, the PTh2 assay is extremely sensitive to the immunoregulatory effects of Mycobacterial extracts and immunosuppressive drugs on primary Th2 cell development. Taken together, this assay provides a standardised method for the identification of the structural and functional properties of proteins relevant to allergenicity, and is a powerful screening tool for novel lead compounds that are effective at inhibiting the primary Th2 response in allergic diseases. •An in vivo assay that detects IL-4 producing CD4 T cells•Primary immune response without multiple immunisations or adjuvants•Highly sensitive and quantitative allowing comparisons between allergens•Independent of the influence of endotoxin•Can measure suppression by pharmacological agents
ISSN:0022-1759
1872-7905
DOI:10.1016/j.jim.2013.05.004