Immunological mechanisms involved in seasonal pollen allergy and allergen-specific immunotherapy

Detta är en avhandling från Uppsala : Acta Universitatis Upsaliensis

Sammanfattning: Th1/Th2-like T-cell responses were studied by stimulating peripheral blood mononuclear cells (PBMCs) with allergens or antigens followed by restimulation with mitogens to induce high cytokine synthesis. Allergen-stimulation in vitro induced Th2-skewed cytokine synthesis by PBMCs from birch-pollen-allergic patients. The IL-4 and IL-13 production correlated with theserum levels of allergen-specific IgE.Allergic patients were treated by conventional birch-pollen-specific immunotherapy (IT).After a short initial fall, there was a significant increase in allergen-specific proliferation andIL-4, IL-5 and IL-10 production by PBMCs when reaching the maintenance dose and duringthe subsequent pollen season. The increase in IL-4 correlated with a temporary increase inspecific serum IgE. The tetanus toxoid-specific IL-5 and IL-10 production was also increased,suggesting that systemic changes in the capacity to produce Th2-like cytokines might occurduring the early phase of IT. There was no indication of an immune deviation from Th2- toTh1/Th0-like immune response to allergens during 18 months of IT. The enhanced prolifera-tive response to allergens was absent in allergic patients after IT indicating that induction ofperipheral T-cell tolerance might be part of the mechanism.A pollen-specific rush IT (RIT) study was performed over three years. RIT was generallywell tolerated and led to significant clinical improvements. A fast increase in total and specificserum IgE during the early months of RIT was noticed followed by decreased levels. SpecificIgG and IgG4 increased continuously over a two-year period. Decreased medication duringthe third year of RIT correlated with the relative decrease in specific IgE.Measuring cytokine synthesis by allergen-stimulated PEMCs and antibody levels in serummay be useful in monitoring immunological responses during IT.

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