Grass tablet sublingual immunotherapy downregulates the聽T_H2 cytokine response followed by regulatory T-cell聽generation

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• 作者：Abel Su谩rez-Fueyo ; Tania Ramos ; Agust铆n Gal谩n ; Lucia Jimeno ; Peter A. Wurtzen ; Alicia Marin ; Consolaci贸n de Frutos ; Carlos Blanco ; Ana C. Carrera ; Domingo Barber ; Rosa Varona
• 关键词：Sublingual immunotherapy ; regulatory T cells ; allergic rhinitis ; IgG4 ; IgE ; IL-4
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：January, 2014
• 年：2014
• 卷：133
• 期：1
• 页码：130-138.e2
• 全文大小：1667 K

文摘

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Background

Sublingual administration of Phleum pratense allergen immunotherapy (SLIT) tablets is a clinically efficient treatment for grass pollen-induced rhinoconjunctivitis. This immunotherapy downregulates T_H2 immune responses, induces tolerogenic pathways, and increases regulatory T cells. However, associated immune response markers of allergen desensitization remain undefined.

Objective

We sought to characterize the kinetics of individual changes in the immunologic response to grass tablet SLIT.

Methods

We evaluated the systemic effects of SLIT in a longitudinal analysis of humoral and cellular immune parameters in peripheral blood samples.

Results

Grass tablet SLIT administration induced a 2-phase systemic humoral and cellular response. The T_H2 response was initially exacerbated and detected as increased allergen-specific IgE (sIgE) and IgG₄ (sIgG₄) levels and an increase in IL-4-producing cells, followed by downregulation of the T_H2 response with a shift toward a T_H1 cytokine profile. T cells with a regulatory phenotype were also elicited. Statistical correlations between immunologic measurements for each patient throughout therapy indicated that T_H2 response downregulation and reduction of the immediate SLIT-induced IgE response were associated with increased allergen-specific IgG₄ synthesis early in therapy. T_H2 response downregulation by month 4 correlated with increased frequency of CD4⁺ T cells with a regulatory phenotype by 12 months.

Conclusion

Changes in sIgE levels after therapy were linked to聽a specific IgG₄ response, and production of blocking antibodies聽correlated with T_H2 response downregulation. Reduced IL-4⁺ cell frequency was linked to an increase in the frequency of CD4⁺ T cells with a regulatory phenotype. Changes in sIgE levels and reduced IL-4 and blocking antibody聽levels could thus be used as indicators of a patient's immune response to therapy.