Factors Influencing the Allergenicity and Adjuvanticity of Allergens

Stephan Deifl; Barbara Bohle

Disclosures

Immunotherapy. 2011;3(7):881-893. 

In This Article

Allergen-specific Immunotherapy

Allergen-specific immunotherapy (SIT) is the only causative treatment for IgE-associated allergy. SIT consists of repeated administration of increasing doses of allergens to allergic patients with the aim of inducing clinical tolerance to natural allergen exposure.[18] Clinically, SIT improves the quality of life of treated individuals and has been shown to reduce both symptoms of allergy and medication use in controlled clinical trials at the population level in a high number of treated individuals.[19,20] SIT is associated with improved tolerance to allergen challenge, with a decrease in immediate-phase and late-phase allergic inflammation. Moreover, SIT prevents the development of new allergic sensitizations and reduces progression of allergic rhinitis to asthma. Of note, SIT modulates the allergic immune response and thereby shows long-term action that exceeds the treatment period.[21,22] Immunologically, SIT increases the ratio of Th1 to Th2 cytokines.[23,24] In addition, the disease-eliciting Th2 response is downregulated, characterized by the reduced proliferative and cytokine responses in response to allergen stimulation in SIT-treated individuals in vitro.[23]In vivo, the reduced allergen-specific T-cell response is mirrored by reduced late-phase responses.[25,26] The downregulation of the allergen-specific Th2 response has been attributed to the appearance of allergen-specific Treg cells that produce IL-10 and/or TGF-β.[24,25,27–29] Both cytokines are important switch factors for B cells and promote the production of Ig class switching to IgA, IgG1 and IgG4.[30,31] Since the levels of allergen-specific IgG4 antibodies rise dramatically during SIT, they have been considered as 'blocking' antibodies that compete with IgE for allergen binding.[32] Consistent with this hypothesis, the removal of IgG4 antibodies from sera of individuals who had received SIT resulted in an almost complete loss of the inhibition of binding of allergen–IgE complexes.[28] In summary, SIT alters the allergen-specific T-cell response from the Th2-like towards a more Th0/1-like response and induces Treg cells, which has consequences for the production of allergen-specific 'blocking' antibodies. Apart from this modulation of the adaptive immune response to allergens, SIT also modulates the function of APCs and effector cells[21] (e.g., reduction of the number of mast cells and their ability to release mediators). The recruitment of eosinophils and neutrophils to sites of allergen exposure is also reduced during SIT.

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