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 effects on asthmatic inflammation are less clear. OBJECTIVE: We sought to determine the dynamics, nature, and immunoregulatory 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.
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 effects on asthmatic inflammation are less clear. OBJECTIVE: We sought to determine the dynamics, nature, and immunoregulatory 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.
Authors: S Hutchison; B S W Choo-Kang; V B Gibson; R V Bundick; A J Leishman; J M Brewer; I B McInnes; P Garside Journal: Clin Exp Immunol Date: 2009-01 Impact factor: 4.330
Authors: N J Daniels; E Hyde; S Ghosh; K Seo; K M Price; K Hoshino; T Kaisho; T Okada; F Ronchese Journal: Mucosal Immunol Date: 2015-06-24 Impact factor: 7.313
Authors: Yi Jia; Katsuyuki Takeda; Junyan Han; Anthony Joetham; Roland A Marcus; Joseph J Lucas; Brian P O'Connor; Erwin W Gelfand Journal: J Immunol Date: 2013-03-18 Impact factor: 5.422