Regulation of allergic airway inflammation by class I-restricted allergen presentation and CD8 T-cell infiltration

Abstract

Background: CD8 T cells are known to respond to exogenous antigens through cross-presentation. The importance of the CD8 cell response in the lung after inhalation of allergen and its\ua0effects on asthmatic inflammation are less clear. Objective: We sought to determine the dynamics, nature, and\ua0immunoregulatory activities of the class I CD8 T-cell response to inhaled allergen. Methods: We studied a murine model of respiratory allergen sensitization, adoptive transfer of transgenic T cells, and flow cytometric analysis of lung infiltrates. Results: Class I-restricted CD8 T cells responded rapidly to inhaled allergen and dominated the acute infiltration of T cells into the lung after secondary exposure. CD8 cells in the lung expressed a type 1 phenotype and suppressed the systemic IgE response to subsequent immunization. Dendritic cells purified from conducting airways or lung tissue were highly efficient at cross-presentation of antigen into the class I pathway after intranasal challenge. Adoptive transfer of transgenic antigen-specific CD8, but not CD4, cells resulted in increased IL-12 levels and reduced IL-13 and IL-5 levels in bronchoalveolar lavage fluid, coupled with substantially reduced airway eosinophilia after repeated allergen inhalation, a process mimicked by intranasal administration of IL-12 and inhibited by anti-IL-12 antibody. Conclusion: The data suggest that CD8 cells specific for inhaled allergens are generated in draining lymph nodes but suppress allergic airway inflammation through induction of IL-12 in the lung during interaction with respiratory dendritic cells. Clinical implications: Novel peptide immunotherapeutics targeting the class I-restricted CD8 T-cell response to allergen represent a promising strategy for extrinsic asthma