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* Immunopathogensis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and
Biomedical Research Institute, Rockville, MD 20852
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases.
2 Address correspondence and reprint requests to Dr. Thomas A. Wynn, Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, 50 South Drive, Room 6154, Mail Stop Code 8003, Bethesda, MD 20892. E-mail address: twynn{at}niaid.nih.gov
3 Abbreviations used in this paper: Treg, regulatory T cell; ABPAS, Alcian blue-periodic acid Schiff; AHR, airway hyperresponsiveness; BAL, bronchoalveolar lavage; rh, recombinant human; rm, recombinant murine; SEA, soluble egg antigen from S. mansoni; S:S, SEA sensitization; S:S:S, SEA sensitization, challenge, and further challenge; tiger, IL-ten ires gfp-enhanced reporter; WT, wild type.
4 The online version of this article contains supplemental material.
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  K. E. Webster, S. Walters, R. E. Kohler, T. Mrkvan, O. Boyman, C. D. Surh, S. T. Grey, and J. Sprent In vivo expansion of T reg cells with IL-2-mAb complexes: induction of resistance to EAE and long-term acceptance of islet allografts without immunosuppression J. Exp. Med., April 13, 2009; 206(4): 751 - 760. [Abstract] [Full Text] [PDF]
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