J W Upham1, J A Denburg, P M O'Byrne. 1. Department of Medicine, University of Western Australia, Perth, Australia, and Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Abstract
BACKGROUND: Dendritic cells (DC) are thought to play a key role in the initiation and maintenance of T cell immunity to inhaled antigens. While the density of DC within the bronchial mucosa is increased in stable asthma, there is little information currently available concerning the effects of allergen inhalation on DC in subjects with asthma. OBJECTIVES: To enumerate changes in the numbers of circulating CD33(+) myeloid DC in asthmatics, before and after allergen challenge. METHODS: Blood DC numbers were enumerated by flow cytometry before and at 3, 6 and 24 h after inhaled allergen and diluent in 10 mild, allergic asthmatic subjects. RESULTS: Blood DC numbers rapidly fell from 3.42 +/- 0.30 x 10(7)/L at baseline, to 2.10 +/- 0.17 x 10(7)/L by 3 h post-challenge (P < 0.01), and remained significantly below baseline values at both 6 and 24 h following allergen challenge. No such changes in DC numbers were noted after diluent challenge. A similar, early fall in circulating lymphocytes was also noted post-allergen challenge, whereas changes in circulating eosinophil and neutrophil numbers occurred more slowly. CONCLUSIONS: A significant proportion of myeloid DC rapidly 'disappear' from the circulation following allergen inhalation, suggesting that margination of circulating myeloid DC, and their recruitment into the airway mucosa, is an important feature of the immune response to inhaled allergen.
BACKGROUND: Dendritic cells (DC) are thought to play a key role in the initiation and maintenance of T cell immunity to inhaled antigens. While the density of DC within the bronchial mucosa is increased in stable asthma, there is little information currently available concerning the effects of allergen inhalation on DC in subjects with asthma. OBJECTIVES: To enumerate changes in the numbers of circulating CD33(+) myeloid DC in asthmatics, before and after allergen challenge. METHODS: Blood DC numbers were enumerated by flow cytometry before and at 3, 6 and 24 h after inhaled allergen and diluent in 10 mild, allergic asthmatic subjects. RESULTS: Blood DC numbers rapidly fell from 3.42 +/- 0.30 x 10(7)/L at baseline, to 2.10 +/- 0.17 x 10(7)/L by 3 h post-challenge (P < 0.01), and remained significantly below baseline values at both 6 and 24 h following allergen challenge. No such changes in DC numbers were noted after diluent challenge. A similar, early fall in circulating lymphocytes was also noted post-allergen challenge, whereas changes in circulating eosinophil and neutrophil numbers occurred more slowly. CONCLUSIONS: A significant proportion of myeloid DC rapidly 'disappear' from the circulation following allergen inhalation, suggesting that margination of circulating myeloid DC, and their recruitment into the airway mucosa, is an important feature of the immune response to inhaled allergen.
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