Regulation of allergen-induced bone marrow eosinophilopoiesis: role of CD4+ and CD8+ T cells

Authors

  • M. Rådinger,

    1. Lung Pharmacology Group, Institite of Medicine, Department of Internal Medicine/Respiratory Medicine and Allergology, Göteborg University, Göteborg, Sweden
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  • A. Bossios,

    1. Lung Pharmacology Group, Institite of Medicine, Department of Internal Medicine/Respiratory Medicine and Allergology, Göteborg University, Göteborg, Sweden
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  • A.-S. Alm,

    1. Lung Pharmacology Group, Institite of Medicine, Department of Internal Medicine/Respiratory Medicine and Allergology, Göteborg University, Göteborg, Sweden
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  • P. Jeurink,

    1. Lung Pharmacology Group, Institite of Medicine, Department of Internal Medicine/Respiratory Medicine and Allergology, Göteborg University, Göteborg, Sweden
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  • Y. Lu,

    1. Lung Pharmacology Group, Institite of Medicine, Department of Internal Medicine/Respiratory Medicine and Allergology, Göteborg University, Göteborg, Sweden
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  • C. Malmhäll,

    1. Lung Pharmacology Group, Institite of Medicine, Department of Internal Medicine/Respiratory Medicine and Allergology, Göteborg University, Göteborg, Sweden
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  • M. Sjöstrand,

    1. Lung Pharmacology Group, Institite of Medicine, Department of Internal Medicine/Respiratory Medicine and Allergology, Göteborg University, Göteborg, Sweden
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  • J. Lötvall

    1. Lung Pharmacology Group, Institite of Medicine, Department of Internal Medicine/Respiratory Medicine and Allergology, Göteborg University, Göteborg, Sweden
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Madeleine Rådinger
Lung Pharmacology Group
Institite of Medicine
Department of Internal Medicine/Respiratory Medicine and Allergology
Göteborg University
Guldhedsgatan 10A
SE 41346 Göteborg
Sweden

Abstract

Background:  The mechanisms of the distant stimulation of the bone marrow (BM) after airway allergen exposure remain largely obscure. T cells have been implicated in allergic airway inflammation but their role in allergen-induced BM eosinophilopoiesis is poorly understood. The aim of this study was to determine the role of CD4+ and CD8+ T cells in allergen-induced BM eosinophilopoiesis.

Methods:  Ovalbumin (OVA)-sensitized wild type (WT), CD4 knockout (CD4−/−) and CD8 knockout (CD8−/−) mice were exposed intranasally to OVA or saline. Bromo-deoxyuridine (BrdU) was used to label newly produced cells. Bone marrow, blood and bronchoalveolar lavage (BAL) were sampled 24 h after the final exposure. Immunostaining for newly produced eosinophils (i.e. BrdU+/MBP+) and BM eosinophil progenitor [CD34+/CD45+/interleukin-5 (IL-5)Ralpha+] cells was performed.

Results:  The number of newly produced BM eosinophils (BrdU+/MBP+ cells) was significantly reduced in allergen exposed CD4−/− or CD8−/− mice compared with allergen exposed WT mice, which was followed by a subsequent decrease in newly produced blood and airway eosinophils. Furthermore, BM eosinophil progenitors were significantly reduced in allergen exposed CD4−/− and CD8−/− mice compared with WT mice. Finally, serum IL-5 and Bronchoalveolar lavage fluid eotaxin-2 levels were abolished in allergen exposed CD4−/− mice to levels seen in saline exposed WT mice.

Conclusions:  These data suggests that both CD4+ and CD8+ T cells have a regulatory role in allergen-induced BM eosinophilopoiesis, whereas CD4+ T cells are obligatory for allergen-induced airway eosinophilia. The subsequent traffic of eosinophils to the airways is likely to be at least partly regulated by a CD4+ T-cell-dependent local airway eotaxin-2 production.

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