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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Peptide immunotherapy is associated with allergen-specific hyporesponsiv...
Peptide immunotherapy is associated with allergen-specific hyporesponsiveness and the induction of IL-10. (A) Cat-allergic asthmatic subjects (n = 6) were challenged intradermally with a mixture of 12 peptides (5 μg each) from the sequence of Fel d 1 or vehicle alone. Lung function was measured by spirometry for 6 hours. Challenges were separated by 14 days or more. Challenge with vehicle (circles) did not significantly modify forced expiratory volume in one second (FEV1). Initial peptide challenge (squares) resulted in an isolated LAR that significantly differed from baseline (P = 0.02 area under the curve; AUC). A second challenge (triangles) with the same dose of peptide was associated with an attenuated or absent LAR. Values are mean of 6 individuals with standard error. (B) Cat-allergic asthmatic subjects underwent intradermal allergen challenge (volar aspect of the forearm) before and after administration of a mixture of 11 peptides in incremental divided doses. Peptide treatment significantly reduced the magnitude of the cutaneous late-phase reaction. (C) Treatment of 16 cat-allergic asthmatic individuals with a mixture of 12 peptides (incremental divided doses) resulted in elevated production of IL-10 by peripheral blood mononuclear cells at both 4–6 weeks and 3–9 months after the completion of treatment. Data presented as median and interquartile range.