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


CONCLUSIONS
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.


CONCLUSIONS
Novel peptide immunotherapeutics targeting the class I-restricted CD8 T-cell response to allergen represent a promising strategy for extrinsic asthma.
Wells
James W
JW
King's College London, UK.
Cowled
Christopher J
CJ
Giorgini
Angela
A
Kemeny
David M
DM
Noble
Alistair
A
D000485:Allergens / Q000276:immunology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology*; D018664:Interleukin-12 / Q000276:immunology*; D018793:Interleukin-13 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D018418:Th2 Cells / Q000276:immunology
D000485:Allergens; D018793:Interleukin-13; D015848:Interleukin-5; D018664:Interleukin-12; D010047:Ovalbumin