The Journal of Experimental Medicine
Keystone Symposia
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Published online 28 November 2005 doi:10.1084/jem.20051166
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 11, 1539-1547
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ARTICLE

 Resolution of airway inflammation and hyperreactivity after in vivo transfer of CD4+CD25+ regulatory T cells is interleukin 10 dependent

Jennifer Kearley1, Jane E. Barker2, Douglas S. Robinson1, and Clare M. Lloyd1

1 Leukocyte Biology Section, Allergy and Clinical Immunology, National Heart and Lung Institute, Faculty of Medicine, Imperial College, SW7 2AZ London, England, UK
2 Discovery BioScience, AstraZeneca R&D Charnwood, LE11 5RH Loughborough, England, UK

CORRESPONDENCE Clare M. Lloyd: c.lloyd{at}imperial.ac.uk

Deficient suppression of T cell responses to allergen by CD4+CD25+ regulatory T cells has been observed in patients with allergic disease. Our current experiments used a mouse model of airway inflammation to examine the suppressive activity of allergen-specific CD4+CD25+ T cells in vivo. Transfer of ovalbumin (OVA) peptide–specific CD4+CD25+ T cells to OVA-sensitized mice reduced airway hyperreactivity (AHR), recruitment of eosinophils, and T helper type 2 (Th2) cytokine expression in the lung after allergen challenge. This suppression was dependent on interleukin (IL) 10 because increased lung expression of IL-10 was detected after transfer of CD4+CD25+ T cells, and regulation was reversed by anti–IL-10R antibody. However, suppression of AHR, airway inflammation, and increased expression of IL-10 were still observed when CD4+CD25+ T cells from IL-10 gene–deficient mice were transferred. Intracellular cytokine staining confirmed that transfer of CD4+CD25+ T cells induced IL-10 expression in recipient CD4+ T cells, but no increase in IL-10 expression was detected in airway macrophages, dendritic cells, or B cells. These data suggest that CD4+CD25+ T cells can suppress the Th2 cell–driven response to allergen in vivo by an IL-10–dependent mechanism but that IL-10 production by the regulatory T cells themselves is not required for such suppression.

Abbreviations used: AHR, airway hyperreactivity; BAL, bronchoalveolar lavage; Cdyn, dynamic compliance; RL, lung resistance.


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