Eosinophils Induce Accumulation of Effector T Cells in Models of Allergic Pulmonary Inflammation

Abstract

BackgroundEosinophil infiltration into the lung and airways is a hallmark of allergic asthma, yet the role of eosinophils in immune regulation of Th2-mediated pulmonary inflammation is poorly defined. Our data suggest a novel role for eosinophils as immune modulators that drive Th2-mediated pulmonary pathologies through activation/recruitment of Tcells and modulation of Th2 cytokines.MethodsTwo independent models of acute allergic inflammation were conducted in mice congenitally devoid of eosinophils (transgenic line: PHIL) and wild type mice. Mice were either sensitized and challenged with ovalbumin (OVA) or adoptively transferred with OVA-specific (OT-II) Th2 polarized T cells and eosinophils followed by challenge with OVA.ResultsPHIL mice that underwent the OVA sensitization/challenge had reduced bronchoalveolar lavage (BAL) levels of Th2 cytokines and reduced pulmonary T cell numbers as compared to wild type mice. Adoptive cell transfer studies using Th2 polarized OT-II T cells and eosinophils demonstrated that only adoptive transfer of both eosinophils and T cells increased BAL Th2 cytokines levels and accumulation of effector T cells (CD62L(-)CD44(+)) in the lungs of allergen-challenged mice.ConclusionsEosinophil effector functions in pulmonary Th2 inflammation likely includes not only destructive effector functions, but also immune regulating roles. The data suggest eosinophils contribute to Th2 inflammation through direct and indirect modulation of Th2 cytokines. More importantly, eosinophils appear to enhance Th2 inflammation through the activation/recruitment of T cells to the lymph nodes and lungs of allergen sensitized/challenged mice, which in turn implicates an expanded role for eosinophils in the onset and maintenance of allergic asthma. BackgroundEosinophil infiltration into the lung and airways is a hallmark of allergic asthma, yet the role of eosinophils in immune regulation of Th2-mediated pulmonary inflammation is poorly defined. Our data suggest a novel role for eosinophils as immune modulators that drive Th2-mediated pulmonary pathologies through activation/recruitment of Tcells and modulation of Th2 cytokines. Eosinophil infiltration into the lung and airways is a hallmark of allergic asthma, yet the role of eosinophils in immune regulation of Th2-mediated pulmonary inflammation is poorly defined. Our data suggest a novel role for eosinophils as immune modulators that drive Th2-mediated pulmonary pathologies through activation/recruitment of Tcells and modulation of Th2 cytokines. MethodsTwo independent models of acute allergic inflammation were conducted in mice congenitally devoid of eosinophils (transgenic line: PHIL) and wild type mice. Mice were either sensitized and challenged with ovalbumin (OVA) or adoptively transferred with OVA-specific (OT-II) Th2 polarized T cells and eosinophils followed by challenge with OVA. Two independent models of acute allergic inflammation were conducted in mice congenitally devoid of eosinophils (transgenic line: PHIL) and wild type mice. Mice were either sensitized and challenged with ovalbumin (OVA) or adoptively transferred with OVA-specific (OT-II) Th2 polarized T cells and eosinophils followed by challenge with OVA. ResultsPHIL mice that underwent the OVA sensitization/challenge had reduced bronchoalveolar lavage (BAL) levels of Th2 cytokines and reduced pulmonary T cell numbers as compared to wild type mice. Adoptive cell transfer studies using Th2 polarized OT-II T cells and eosinophils demonstrated that only adoptive transfer of both eosinophils and T cells increased BAL Th2 cytokines levels and accumulation of effector T cells (CD62L(-)CD44(+)) in the lungs of allergen-challenged mice. PHIL mice that underwent the OVA sensitization/challenge had reduced bronchoalveolar lavage (BAL) levels of Th2 cytokines and reduced pulmonary T cell numbers as compared to wild type mice. Adoptive cell transfer studies using Th2 polarized OT-II T cells and eosinophils demonstrated that only adoptive transfer of both eosinophils and T cells increased BAL Th2 cytokines levels and accumulation of effector T cells (CD62L(-)CD44(+)) in the lungs of allergen-challenged mice. ConclusionsEosinophil effector functions in pulmonary Th2 inflammation likely includes not only destructive effector functions, but also immune regulating roles. The data suggest eosinophils contribute to Th2 inflammation through direct and indirect modulation of Th2 cytokines. More importantly, eosinophils appear to enhance Th2 inflammation through the activation/recruitment of T cells to the lymph nodes and lungs of allergen sensitized/challenged mice, which in turn implicates an expanded role for eosinophils in the onset and maintenance of allergic asthma. Eosinophil effector functions in pulmonary Th2 inflammation likely includes not only destructive effector functions, but also immune regulating roles. The data suggest eosinophils contribute to Th2 inflammation through direct and indirect modulation of Th2 cytokines. More importantly, eosinophils appear to enhance Th2 inflammation through the activation/recruitment of T cells to the lymph nodes and lungs of allergen sensitized/challenged mice, which in turn implicates an expanded role for eosinophils in the onset and maintenance of allergic asthma.