Nature Medicine8, 1024 - 1032 (2002)
Published online: 29 July 2002; Corrected online: 26 August 2002 | doi:10.1038/nm745
Antigen-specific regulatory T cells develop via the ICOS−ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity
Omid Akbari1, Gordon J. Freeman3, Everett H. Meyer1, Edward A. Greenfield3, Tammy T. Chang4, Arlene H. Sharpe4, Gerald Berry2, Rosemarie H. DeKruyff1
& Dale T. Umetsu1
1
Division of Immunology and Allergy, Department of Pediatrics, School of Medicine, Stanford University, Stanford, California, USA
2
Department of Pathology, School of Medicine, Stanford University, Stanford, California, USA
3
Department of Adult Oncology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
4
Immunology Research Division, Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA
Asthma is caused by T-helper cell 2 (Th2)-driven immune responses, but the immunological mechanisms that protect against asthma development are poorly understood. T-cell tolerance, induced by respiratory exposure to allergen, can inhibit the development of airway hyperreactivity (AHR), a cardinal feature of asthma, and we show here that regulatory T (TR) cells can mediate this protective effect. Mature pulmonary dendritic cells in the bronchial lymph nodes of mice exposed to respiratory allergen induced the development of TR cells, in a process that required T-cell costimulation via the inducible costimulator (ICOS)−ICOS-ligand pathway. The TR cells produced IL-10, and had potent inhibitory activity; when adoptively transferred into sensitized mice,* TR cells blocked the development of AHR. Both the development and the inhibitory function of regulatory cells were dependent on the presence of IL-10 and on ICOS−ICOS-ligand interactions. These studies demonstrate that TR cells and the ICOS−ICOS-ligand signaling pathway are critically involved in respiratory tolerance and in downregulating pulmonary inflammation in asthma.
*There was an error in the AOP version of this article. The sentence in the abstract that read The TR cells produced IL-10, and had potent inhibitory activity; when adoptively transferred into sensitized mouse TR cells, blocked the development of AHR was worded incorrectly. The following sentence is correct: The TR cells produced IL-10, and had potent inhibitory activity; when adoptively transferred into sensitized mice, TR cells blocked the development of AHR. This has been corrected in the HTML and the PDF. We regret this error.
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