@article {542711,
	title = {Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity.},
	journal = {Nat Med},
	volume = {8},
	number = {9},
	year = {2002},
	month = {2002 Sep},
	pages = {1024-32},
	abstract = {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 (T(R)) 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 T(R) cells, in a process that required T-cell costimulation via the inducible costimulator (ICOS-ICOS-ligand pathway. The T(R) cells produced IL-10, and had potent inhibitory activity; when adoptively transferred into sensitized mice, T(R) 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 T(R) cells and the ICOS-ICOS-ligand signaling pathway are critically involved in respiratory tolerance and in downregulating pulmonary inflammation in asthma.},
	keywords = {Allergens, Animals, Antigens, Antigens, Differentiation, T-Lymphocyte, Asthma, Bronchial Hyperreactivity, Bronchoalveolar Lavage Fluid, Inducible T-Cell Co-Stimulator Ligand, Inducible T-Cell Co-Stimulator Protein, Interleukin-10, Ligands, Mice, Mice, Inbred BALB C, Mice, Transgenic, Ovalbumin, Proteins, T-Lymphocytes},
	issn = {1078-8956},
	doi = {10.1038/nm745},
	author = {Akbari, Omid and Freeman, Gordon J and Meyer, Everett H and Greenfield, Edward A and Chang, Tammy T and Sharpe, Arlene H and Berry, Gerald and DeKruyff, Rosemarie H and Umetsu, Dale T}
}
