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

Wells, James W., Cowled, Christopher J., Giorgini, Angela, Kemeny, David M. and Noble, Alistair (2007) Regulation of allergic airway inflammation by class I-restricted allergen presentation and CD8 T-cell infiltration. Journal of Allergy and Clinical Immunology, 119 1: 226-234. doi:10.1016/j.jaci.2006.09.004

Author Wells, James W.
Cowled, Christopher J.
Giorgini, Angela
Kemeny, David M.
Noble, Alistair
Title Regulation of allergic airway inflammation by class I-restricted allergen presentation and CD8 T-cell infiltration
Journal name Journal of Allergy and Clinical Immunology   Check publisher's open access policy
ISSN 0091-6749
Publication date 2007-01
Sub-type Article (original research)
DOI 10.1016/j.jaci.2006.09.004
Volume 119
Issue 1
Start page 226
End page 234
Total pages 9
Place of publication Philadelphia, PA, United States
Publisher Mosby
Language eng
Formatted abstract

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.

We sought to determine the dynamics, nature, and immunoregulatory activities of the class I CD8 T-cell response to inhaled allergen.

We studied a murine model of respiratory allergen sensitization, adoptive transfer of transgenic T cells, and flow cytometric analysis of lung infiltrates.

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.

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.
Keyword CD8(+) T lymphocytes
Dendritic Cells
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
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