Tregs and allergic disease
Douglas S. Robinson, Mark Larché, Stephen R. Durham
Douglas S. Robinson, Mark Larché, Stephen R. Durham
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Tregs and allergic disease

Abstract

Allergic diseases such as asthma, rhinitis, and eczema are increasing in prevalence and affect up to 15% of populations in Westernized countries. The description of Tregs as T cells that prevent development of autoimmune disease led to considerable interest in whether these Tregs were also normally involved in prevention of sensitization to allergens and whether it might be possible to manipulate Tregs for the therapy of allergic disease. Current data suggest that Th2 responses to allergens are normally suppressed by both CD4+CD25+ Tregs and IL-10 Tregs. Furthermore, suppression by these subsets is decreased in allergic individuals. In animal models, Tregs could be induced by high- or low-dose inhaled antigen, and prior induction of such Tregs prevented subsequent development of allergen sensitization and airway inflammation in inhaled challenge models. For many years, allergen-injection immunotherapy has been used for the therapy of allergic disease, and this treatment may induce IL-10 Tregs, leading to both suppression of Th2 responses and a switch from IgE to IgG4 antibody production. Improvements in allergen immunotherapy, such as peptide therapy, and greater understanding of the biology of Tregs hold great promise for the treatment and prevention of allergic disease.

Authors

Douglas S. Robinson, Mark Larché, Stephen R. Durham

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Potential mechanisms of conventional allergen immunotherapy. High-dose a...
Potential mechanisms of conventional allergen immunotherapy. High-dose allergen exposure during immunotherapy results in both immune deviation of Th2 responses in favor of a Th0/Th1 response and in the generation of IL-10– and TGF-β–producing CD4+CD25+ T cells, possibly Tregs. IFN-γ–induced activation of bystander macrophages and/or other cells represents an alternative source of these inhibitory cytokines. During subsequent natural environmental exposure to allergens, the activation and/or maintenance of the usual atopic Th2 T cell response is inhibited. Additionally, these cytokines induce preferential switching of B cell responses in favor of IgG and IgG4 antibodies (and possibly IgA antibodies under the influence of TGF-β). IgG may also inhibit IgE-facilitated allergen binding to antigen-presenting cells with subsequent downregulation of IgE-dependent Th2 T lymphocyte responses. Blue arrows represent immune response pathway to natural exposure (low-doses Ag and IgE); green arrows represent immune response pathway to immunotherapy (high-dose Ag); red blocked lines represent inhibition (high-dose Ag); dotted lines represent possible means of action not yet proven.