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The Journal of Immunology, 2007, 178: 1433-1442.
Copyright © 2007 by The American Association of Immunologists, Inc.

Naturally Occurring Lung CD4+CD25+ T Cell Regulation of Airway Allergic Responses Depends on IL-10 Induction of TGF-beta1

Anthony Joetham, Katsuyuki Takada, Christian Taube, Nobuaki Miyahara, Satoko Matsubara, Toshiyuki Koya, Yeong-Ho Rha, Azzeddine Dakhama and Erwin W. Gelfand2

Department of Pediatrics, Division of Cell Biology, National Jewish Medical and Research Center, Denver, CO 80206

Peripheral tolerance to allergens is mediated in large part by the naturally occurring lung CD4+CD25+ T cells, but their effects on allergen-induced airway responsiveness have not been well defined. Intratracheal, but not i.v., administration of naive lung CD4+CD25+ T cells before allergen challenge of sensitized mice, similar to the administration of the combination of rIL-10 and rTGF-beta, resulted in reduced airway hyperresponsiveness (AHR) and inflammation, lower levels of Th2 cytokines, higher levels of IL-10 and TGF-beta, and less severe lung histopathology. Significantly, CD4+CD25+ T cells isolated from IL-10–/– mice had no effect on AHR and inflammation, but when incubated with rIL-10 before transfer, suppressed AHR, and inflammation, and was associated with elevated levels of bronchoalveolar lavage TGF-beta levels. By analogy, anti-TGF-beta treatment reduced regulatory T cell activity. These data identify naturally occurring lung CD4+CD25+ T cells as capable of regulating lung allergic responses in an IL-10- and TGF-beta-dependent manner.

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 National Institutes of Health Grants HL-36577 and HL-61005 and by Environmental Protection Agency Grant R825702.

2 Address correspondence and reprint requests to Dr. Erwin W. Gelfand, Department of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206. E-mail address: gelfande{at}njc.org

3 Abbreviations used in this paper: AHR, airway hyperresponsiveness; Treg, regulatory T cell; Foxp3, forkhead box p3; MNC, mononuclear cell; RL, lung resistance; MCh, methacholine; BAL, bronchoalveolar lavage; PAS, periodic acid-Schiff; WT, wild type.




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