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Coexpression of TGF-β1 and IL-10 Enables Regulatory T Cells to Completely Suppress Airway Hyperreactivity¹

Katrin Presser^*, Dorothee Schwinge^*, Michael Wegmann, Samuel Huber^*, Steffen Schmitt, Alexander Quaas, Joachim H. Maxeiner^¶, Susetta Finotto^¶, Ansgar W. Lohse^*, Manfred Blessing^|| and Christoph Schramm^2,*

^* I. Department of Medicine and Institute for Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Institute for Clinical Chemistry and Molecular Diagnostics, Philipps-University, Marburg, Germany; NMFZ and ^¶ I. Department of Medicine, Johannes Gutenberg University, Mainz, Germany; and ^|| BBZ, University Leipzig, Leipzig, Germany

In allergic airway disease, Treg may play an important role in the modulation of airway hyperreactivity (AHR) and inflammation. We therefore investigated the therapeutic potential of Treg in an Ag-dependent murine asthma model. We here describe that AHR can be completely suppressed by adoptive transfer of Treg overexpressing active TGF-β1. Using mice with impaired TGF-β signaling in T cells, we could demonstrate that TGF-β signaling in recipient effector T cells or transferred Treg themselves is not required for the protective effects on AHR. However, the expression of IL-10 by Treg was found to be essential for the suppression of AHR, since Treg overexpressing active TGF-β1 but deficient in IL-10 lacked protective effects. Airway inflammation could not be significantly suppressed by wild-type or transgenic Treg. In conclusion, modulation of cytokine expression by Treg may have therapeutic potential for the treatment of AHR in asthma. The mechanisms of the effects of Treg on airway inflammation require further clarification.

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 work was supported by Deutsche Forschungsgemeinschaft SCHR781/1-1 and 1-2 and the Hans-Werner Otto Foundation.

² Address correspondence and reprint requests to Dr. Christoph Schramm, University Medical Center, Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. E-mail address: cschramm{at}uke.uni-hamburg.de

³ Abbreviations used in this paper: Treg, regulatory T cell; AHR, airway hyperreactivity; BALF, bronchoalveolar lavage fluid; MCh, methacholine; dTG, double transgenic; n.s., nonsignificant; RI, lung resistance; EF, expiratory flow; ASM, airway smooth muscle cell.