Mechanisms of allergen-specific immunotherapy

Cezmi A Akdis,Mübeccel Akdis

doi:10.1016/j.jaci.2010.11.030

Cezmi A Akdis, Mübeccel Akdis

Open Access

https://doi.org/10.1016/j.jaci.2010.11.030

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Abstract

Allergen-specific immunotherapy has been used for 100 years as a desensitizing therapy for allergic diseases and represents the potentially curative and specific method of treatment. The mechanisms of action of allergen-specific immunotherapy include the very early desensitization effects, modulation of T-and B-cell responses and related antibody isotypes, and migration of eosinophils, basophils, and mast cells to tissues, as well as release of their mediators. Regulatory T (Treg) cells have been identified as key regulators of immunologic processes in peripheral tolerance to allergens. Skewing of allergen-specific effector T cells to a regulatory phenotype appears as a key event in the development of healthy immune response to allergens and successful outcome in patients undergoing allergen-specific immunotherapy. Naturally occurring forkhead box protein 3-positive CD4(+)CD25(+) Treg cells and inducible T(R)1 cells contribute to the control of allergen-specific immune responses in several major ways, which can be summarized as suppression of dendritic cells that support the generation of effector T cells; suppression of effector T(H)1, T(H)2, and T(H)17 cells; suppression of allergen-specific IgE and induction of IgG4; suppression of mast cells, basophils, and eosinophils; and suppression of effector T-cell migration to tissues. New strategies for immune intervention will likely include targeting of the molecular mechanisms of allergen tolerance and reciprocal regulation of effector and Treg cell subsets.

Highlights

The immune system is a complex interactive network with the capacity of protecting the host from a number of pathogens while keeping a state of tolerance to self and innocuous non-self antigens
The induction of peripheral T cell tolerance and promotion of the formation of regulatory T-cells are key mechanisms in allergen-SIT. Both FOXP3+CD4+CD25+ regulatory T (Treg) cells and inducible IL-10- and TGF-b-producing type 1 Treg (Tr1) cells may prevent the development of allergic diseases and play a role in successful allergen-SIT and healthy immune response via several mechanisms
Knowledge of these molecular basis is crucial in the understanding the regulation of immune responses and their possible therapeutic targets in allergic diseases

Summary

Background

The immune system is a complex interactive network with the capacity of protecting the host from a number of pathogens while keeping a state of tolerance to self and innocuous non-self antigens. During the development of allergic diseases, effector Th2 cells produce traditional Th2 cytokines such as IL-4, IL-5, IL-9 and IL-13 [11,12], and novel cytokines with proinflammatory functions, such as IL25, IL-31 and IL-33 [13,14,15,16,17,18,19] These cytokines induce allergen-specific IgE, eosinophilia, mucus production and the recruitment of inflammatory cells to inflamed tissues. Mechanisms of allergen-specific immunotherapy T cell regulation Since allergic diseases are Th2 driven, but much rather form complex immune disorders, the aim of allergen SIT is to induce the peripheral T cell tolerance, modulate the thresholds for mast cell and basophil activation and decrease IgE-mediated histamine release [29] (Figure 1 and 2). This type of time regime is being investigated in SLIT [107]

Conclusions

12. Akdis M

38. Chatila TA

67. Fujimoto M