Background: Allergen-specific immunotherapy (SIT) is known to affect the allergen-specific T helper cell (Th2/Th1) balance and to induce T regulatory (Treg) cells. These observations have usually been made during the first treatment year and often without symptom monitoring. This study was performed to investigate allergen-induced Th2 (IL-4, IL-5)-, Th1 [IFN-γ, IL-18, signalling lymphocytic activation molecule (SLAM)]- and Treg (IL-10)-type immune responses in peripheral blood mononuclear cells (PBMC) and their association with symptom improvement in allergic rhinitis patients after 3 years of SIT. Methods: Twenty patients were treated with SIT and 8 patients were studied as untreated controls. PBMC were collected before and after 1 and 3 years of SIT and stimulated with specific allergen. Cytokine and SLAM mRNA expression was determined by TaqMan® RT-PCR. Symptoms were recorded yearly using visual analogue scale (VAS) scoring. Results: IL-18, SLAM and IL-10 mRNA expression increased after 3 years of SIT, with a peak at 1 year, whereas IL-5 mRNA expression transiently decreased and IFN-γ mRNA expression transiently increased after 1 year of SIT. The increases in IL-18 and SLAM expression were not associated with symptom improvement, whereas decreases in both IL-4 expression and the IL-4/IFN-γ ratio after 1 year of SIT were found in patients with a good therapeutic outcome (>40 percentage unit reduction in VAS). Conclusions: SIT has long-term effects on allergen-specific immune responses. The induced Treg- and Th1-type responses persist over 3 years of SIT, whereas Th2-type responses are transiently decreased only during early therapy.

Keywords:
Pollen allergy, Allergic rhinitis, Specific immunotherapy, Cytokines, Signalling lymphocytic activation molecule, Th1 cells, Th2 cells, T regulatory cells
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