Specific CD8 T cells in IgE-mediated allergy correlate with allergen dose and allergic phenotype

Rationale: Studies in humans and rodents have indicated a causative role for CD8 ⁺ T cells in IgE-mediated allergic inflammation, but their function is still controversial. Objectives: Toanalyze the role of allergen-specific CD8 ⁺ T cells during the development of allergic airway inflammation in two parallel but diverging outcome models. Methods: We used H2-Kb SIINFEKL (OVA _257-264) multimers to analyze induction, natural distribution, and phenotype of allergen-specific CD8 ⁺ T cells in amurine C57BL/6 model of ovalbumin (OVA)-induced allergic airway inflammation using low-dose or high-dose OVA sensitization. Measurements and Main Results: The low-dose protocol was characterized by a significant induction of total and OVA-specific IgE, eosinophilic airway inflammation, IL-4 levels in bronchoalveolar lavage fluid. And significant alterations in lung function. The high dose protocol was characterizedbya significant reductionof theallergicphenotype. Using OVA _257-264 H2-Kb multimers, we observed lung and airway infiltrating OVA-specific CD8 ⁺ T cells showing an effector/effectormemory phenotype. The high-dose protocol caused significantly higher infiltration of allergen-specific CD8 ⁺ cells to the airways and enhanced their cytotoxicity. Adoptive transferwith CD8 ⁺ T cells from transgenic OT-I mice to TAP1 ^-/- or wild-type mice showed their migration to the lungs and TAP1-dependent proliferation after OVA aerosol exposure. TAP1 ^-/- mice defective in CD8 ⁺ T cells showed exacerbated symptoms in the low-dose sensitizationmodel. Conclusions: Allergen-specific CD8 ⁺ T cells seem to protect from allergic inflammation in the lungs. Their number, which is dependent on the sensitization dose, appears to be a critical predictor for the severity of the allergic phenotype.