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Antigen Specificity Is not Required for Modulation of Lung Allergic Responses by Naturally Occurring Regulatory T Cells¹

Division of Cell Biology, Department of Pediatrics, National Jewish Health, Denver, CO 80206

Naturally occurring Foxp3⁺CD4⁺CD25⁺ T cells isolated from lungs of naive mice regulate lung allergic airway hyperresponsiveness, inflammation, levels of Th2 cytokines, and mucus production. OVA-specific (βTCR⁺) CD4⁺CD25⁺ T cells suppressed ragweed-induced airway hyperresponsiveness and inflammation as did anti-TCR-treated OVA-specific CD4⁺CD25⁺ T cells, suggesting that Ag-specificity was not required for expression of regulatory activities. Suppression was associated with increased levels of IL-10 and TGF-β; decreased levels of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid; and reduced recruitment and activation of CD8⁺ T cells in the airways. Following intratracheal administration, OVA-specific CD4⁺CD25⁺ T cells were identified in both the airway lumens and lung parenchyma, and in some instances in close proximity to host CD8⁺ T cells. These results demonstrate that the regulatory activities of naturally occurring Foxp3⁺CD4⁺CD25⁺ T cells on lung allergic responses are Ag-nonspecific and thus, independent of Ag-specific recognition.

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, HL-61005, and AI-77609 and by EPA Grant R825702. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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

³ Abbreviations used in this paper: nTreg, naturally occurring CD4⁺CD25⁺ regulatory T cell; AHR, airway hyperresponsiveness; MHC I, MHC class I; WT, wild type; RW, ragweed; R_L, lung resistance; BAL, bronchoalveolar lavage.

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The JI 2009 183: 1501-1502. [Full Text]