Abstract |
Regulatory T cells (Treg) play a decisive role in many diseases including asthma and allergen-induced lung inflammation. However, little progress has been made developing new therapeutic strategies for pulmonary disorders. In the current study we demonstrate that cytokine:antibody complexes of IL-2 and anti-IL-2 mAb reduce the severity of allergen-induced inflammation in the lung by expanding Tregs in vivo. Unlike rIL-2 or anti-IL-2 mAb treatment alone, IL-2:anti-IL-2 complexes dampened airway inflammation and eosinophilia while suppressing IL-5 and eotaxin-1 production. Mucus production, airway hyperresponsiveness to methacholine, and parenchymal tissue inflammation were also dramatically reduced following IL-2:anti-IL-2 treatment. The suppression in allergic airway disease was associated with a marked expansion of Tregs (IL-10(+)CD4(+)CD25(+) and Foxp3(+)CD4(+)CD25(+)) in the tissues, with a corresponding decrease in effector T cell responses. The ability of IL-2:anti-IL-2 complexes to suppress airway inflammation was dependent on Treg-derived IL-10, as IL-10(+/+), but not IL-10(-/-) Tregs, were capable of mediating the suppression. Furthermore, a therapeutic protocol using a model of established airway allergy highlighted the ability of IL-2:anti-IL-2 complexes to expand Tregs and prevent successive airway inflammation and airway hyperresponsiveness. This study suggests that endogenous Treg therapy may be a useful tool to combat the rising incidence of allergic airway disease.
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Authors | Mark S Wilson, John T Pesce, Thirumalai R Ramalingam, Robert W Thompson, Allen Cheever, Thomas A Wynn |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 181
Issue 10
Pg. 6942-54
(Nov 15 2008)
ISSN: 1550-6606 [Electronic] United States |
PMID | 18981114
(Publication Type: Journal Article, Research Support, N.I.H., Intramural)
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Chemical References |
- Antibodies, Monoclonal
- Antigen-Antibody Complex
- Interleukin-2
- Interleukin-10
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Topics |
- Animals
- Antibodies, Monoclonal
(immunology)
- Antigen-Antibody Complex
(immunology)
- Enzyme-Linked Immunosorbent Assay
- Female
- Flow Cytometry
- Immunotherapy
(methods)
- Inflammation
(prevention & control)
- Interleukin-10
- Interleukin-2
(immunology)
- Mice
- Respiratory Hypersensitivity
(immunology, prevention & control)
- Reverse Transcriptase Polymerase Chain Reaction
- T-Lymphocytes, Regulatory
(immunology)
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