Clinical & Experimental Allergy

Airway generation-specific differences in the spatial distribution of immune cells and cytokines in allergen-challenged rhesus monkeys

Authors

  • L. A. Miller,

    1. Center for Comparative Respiratory Biology and Medicine and the California Regional Primate Research Center, University of California, Davis, CA
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  • S. D. Hurst,

    1. DNAX Research Institute, Palo Alto, CA
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    • 1Department of Immunology, Genentech, One DNA Way, South San Francisco, CA 94080.

  • R. L. Coffman,

    1. DNAX Research Institute, Palo Alto, CA
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    • 2Dynavax Technologies, 717 Potter Street, Suite 100, Berkeley, CA 94710.

  • N. K. Tyler,

    1. Center for Comparative Respiratory Biology and Medicine and the California Regional Primate Research Center, University of California, Davis, CA
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  • M. Y. Stovall,

    1. Center for Comparative Respiratory Biology and Medicine and the California Regional Primate Research Center, University of California, Davis, CA
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  • D. L. Chou,

    1. Center for Comparative Respiratory Biology and Medicine and the California Regional Primate Research Center, University of California, Davis, CA
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  • L. F. Putney,

    1. Center for Comparative Respiratory Biology and Medicine and the California Regional Primate Research Center, University of California, Davis, CA
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  • L. J. Gershwin,

    1. Center for Comparative Respiratory Biology and Medicine and the California Regional Primate Research Center, University of California, Davis, CA
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  • E. S. Schelegle,

    1. Center for Comparative Respiratory Biology and Medicine and the California Regional Primate Research Center, University of California, Davis, CA
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  • C. G. Plopper,

    1. Center for Comparative Respiratory Biology and Medicine and the California Regional Primate Research Center, University of California, Davis, CA
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  • D. M. Hyde

    1. Center for Comparative Respiratory Biology and Medicine and the California Regional Primate Research Center, University of California, Davis, CA
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Lisa A. Miller, Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA. E-mail: lmiller@ucdavis.edu

Summary

Background Accumulation of immune cell populations and their cytokine products within tracheobronchial airways contributes to the pathogenesis of allergic asthma. It has been postulated that peripheral regions of the lung play a more significant role than proximal airways with regard to inflammatory events and airflow obstruction.

Objective To determine whether immune cell populations and associated cytokines are uniformly distributed throughout the conducting airway tree in a non-human primate model of allergic asthma.

Methods We used a stereologic approach with a stratified sampling scheme to measure the volume density of immune cells within the epithelium and interstitium of trachea and 4–5 intrapulmonary airway generations from house dust mite (HDM) (Dermatophagoides farinae)-challenged adult monkeys. In conjunction with immune cell distribution profiles, mRNA levels for 21 cytokines/chemokines and three chemokine receptors were evaluated at four different airway generations from microdissected lungs.

Results In HDM-challenged monkeys, the volume of CD1a+ dendritic cells, CD4+ T helper lymphocytes, CD25+ cells, IgE+ cells, eosinophils, and proliferating cells were significantly increased within airways. All five immune cell types accumulated within airways in unique patterns of distribution, suggesting compartmentalized responses with regard to trafficking. Although cytokine mRNA levels were elevated throughout the conducting airway tree of HDM-challenged animals, the distal airways (terminal and respiratory bronchioles) exhibited the most pronounced up-regulation.

Conclusion These findings demonstrate that key effector immune cell populations and cytokines associated with asthma differentially accumulate within distinct regions and compartments of tracheobronchial airways from allergen-challenged primates.

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