ToxSci Advance Access originally published online on May 29, 2008
Toxicological Sciences 2008 105(1):188-199; doi:10.1093/toxsci/kfn106
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Nonredundant Functions of 
β and 
T Cells in Acrolein-Induced Pulmonary Pathology
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* Department of Environmental Health, Division of Environmental Genetics and Molecular Toxicology
Department of Internal Medicine, Division of Pulmonary and Critical Care
Department of Environmental Health, Division of Biostatistics, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45267
1 To whom correspondence should be addressed at Division of Environmental Genetics and Molecular Toxicology, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0056. Fax: (513) 558-0925. E-mail: michael.borchers{at}uc.edu.
Received April 11, 2008; accepted May 22, 2008
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Abstract |
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Acrolein exposure represents a significant human health hazard. Repeated acrolein exposure causes the accumulation of monocytes/macrophages and lymphocytes, mucous cell metaplasia, and epithelial injury. Currently, the mechanisms that control these events are unclear, and the relative contribution of T-cell subsets to pulmonary pathologies following repeated exposures to irritants is unknown. To examine whether lymphocyte subpopulations regulate inflammation and epithelial cell pathology, we utilized a mouse model of pulmonary pathology induced by repeated acrolein exposures. The role of lymphocyte subsets was examined by utilizing transgenic mice genetically deficient in either 
β T cells or 
T cells, and changes in cellular, molecular, and pathologic outcomes associated with repeated inhalation exposure to 2.0 and 0.5 ppm acrolein were measured. To examine the potential functions of lymphocyte subsets, we purified these cells from the lungs of mice repeatedly exposed to 2.0 ppm acrolein, isolated and amplified messenger RNA, and performed microarray analysis. Our data demonstrate that β T cells are required for macrophage accumulation, whereas T cells are critical regulators of epithelial cell homeostasis, as identified by epithelial cell injury and apoptosis, following repeated acrolein exposure. This is supported by microarray analyses that indicated the T-cell subsets are unique in their gene expression profiles following acrolein exposures. Microarray analyses identified several genes that may contribute to phenotypes mediated by T-cell subpopulations including those involved in cytokine receptor signaling, chemotaxis, growth factor production, lymphocyte activation, and apoptosis. These data provide strong evidence that T-cell subpopulations in the lung are major determinants of pulmonary pathology and highlight the advantages of dissecting their effector functions in response to toxicant exposures.
Key Words: inflammation; lung injury; macrophage; acrolein; microarray.