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Lauren Cohn^*,, Robert J. Homer^,||, Anthony Marinov^*, John Rankin^¶, and Kim Bottomly^*,**

From the ^* Section of Immunobiology and Section of Pulmonary and Critical Care Medicine, Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520; ^|| Pathology and Laboratory Medicine Service and ^¶ Section of Pulmonary Medicine, Veterans Administration, Connecticut Health Care System, West Haven, Connecticut 06516; and the ^** Howard Hughes Medical Institute, New Haven, Connecticut 06536

Airway inflammation is believed to stimulate mucus production in asthmatic patients. Increased mucus secretion is an important clinical symptom and contributes to airway obstruction in asthma. Activated CD4 Th1 and Th2 cells have both been identified in airway biopsies of asthmatics but their role in mucus production is not clear. Using CD4 T cells from mice transgenic for the OVA-specific TCR, we studied the role of Th1 and Th2 cells in airway inflammation and mucus production. Airway inflammation induced by Th2 cells was comprised of eosinophils and lymphocytes; features found in asthmatic patients. Additionally, there was a marked increase in mucus production in mice that received Th2 cells and inhaled OVA, but not in mice that received Th1 cells. However, OVA-specific Th2 cells from IL-4–deficient mice were not recruited to the lung and did not induce mucus production. When this defect in homing was overcome by administration of TNF-, IL-4 –/– Th2 cells induced mucus as effectively as IL-4 +/+ Th2 cells. These studies establish a role for Th2 cells in mucus production and dissect the effector functions of IL-4 in these processes. These data suggest that IL-4 is crucial for Th2 cell recruitment to the lung and for induction of inflammation, but has no direct role in mucus production.

¹ Abbreviations used in this paper: BAL, bronchoalveolar lavage; DPAS, diastase-periodic acid-Schiff; HMI, histologic mucus index; pOVA^323-339, OVA peptide 323-339.

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• TOMKINSON, A., CIESLEWICZ, G., DUEZ, C., LARSON, K. A., LEE, J. J., GELFAND, E. W. (2001). Temporal Association between Airway Hyperresponsiveness and Airway Eosinophilia in Ovalbumin-Sensitized Mice. Am. J. Respir. Crit. Care Med. 163: 721-730 [Abstract] [Full Text]  
• Wang, S., Fan, Y., Han, X., Yang, J., Bilenki, L., Yang, X. (2001). IL-12-Dependent Vascular Cell Adhesion Molecule-1 Expression Contributes to Airway Eosinophilic Inflammation in a Mouse Model of Asthma-Like Reaction. J. Immunol. 166: 2741-2749 [Abstract] [Full Text]  
• Cohn, L., Herrick, C., Niu, N., Homer, R. J., Bottomly, K. (2001). IL-4 Promotes Airway Eosinophilia by Suppressing IFN-{{gamma}} Production: Defining a Novel Role for IFN-{{gamma}} in the Regulation of Allergic Airway Inflammation. J. Immunol. 166: 2760-2767 [Abstract] [Full Text]  
• Jember, A. G.-H., Zuberi, R., Liu, F.-T., Croft, M. (2001). Development of Allergic Inflammation in a Murine Model of Asthma Is Dependent on the Costimulatory Receptor Ox40. JEM 193: 387-392 [Abstract] [Full Text]  
• Lloyd, C. M., Gonzalo, J.-A., Nguyen, T., Delaney, T., Tian, J., Oettgen, H., Coyle, A. J., Gutierrez-Ramos, J.-C. (2001). Resolution of Bronchial Hyperresponsiveness and Pulmonary Inflammation Is Associated with IL-3 and Tissue Leukocyte Apoptosis. J. Immunol. 166: 2033-2040 [Abstract] [Full Text]  
• Keen, J. C., Sholl, L., Wills-Karp, M., Georas, S. N. (2001). Preferential Activation of Nuclear Factor of Activated T Cells c Correlates with Mouse Strain Susceptibility to Allergic Responses and Interleukin-4 Gene Expression. Am. J. Respir. Cell Mol. Bio. 24: 58-65 [Abstract] [Full Text]  
• Shim, J. J., Dabbagh, K., Ueki, I. F., Dao-Pick, T., Burgel, P.-R., Takeyama, K., Tam, D. C.-W., Nadel, J. A. (2001). IL-13 induces mucin production by stimulating epidermal growth factor receptors and by activating neutrophils. Am. J. Physiol. Lung Cell. Mol. Physiol. 280: L134-L140 [Abstract] [Full Text]  
• Wang, Z., Zheng, T., Zhu, Z., Homer, R. J., Riese, R. J., Chapman, H. A. Jr., Shapiro, S. D., Elias, J. A. (2000). Interferon {gamma} Induction of Pulmonary Emphysema in the Adult Murine Lung. JEM 192: 1587-1600 [Abstract] [Full Text]  
• Tesfaigzi, Y., Fischer, M. J., Martin, A. J., Seagrave, J. (2000). Bcl-2 in LPS- and allergen-induced hyperplastic mucous cells in airway epithelia of Brown Norway rats. Am. J. Physiol. Lung Cell. Mol. Physiol. 279: L1210-L1217 [Abstract] [Full Text]  
• Pan, Z.-Z., Parkyn, L., Ray, A., Ray, P. (2000). Inducible lung-specific expression of RANTES: preferential recruitment of neutrophils. Am. J. Physiol. Lung Cell. Mol. Physiol. 279: L658-L666 [Abstract] [Full Text]  
• Wang, J., Homer, R. J., Chen, Q., Elias, J. A. (2000). Endogenous and Exogenous IL-6 Inhibit Aeroallergen-Induced Th2 Inflammation. J. Immunol. 165: 4051-4061 [Abstract] [Full Text]  
• Wang, J., Homer, R. J., Hong, L., Cohn, L., Lee, C. G., Jung, S., Elias, J. A. (2000). IL-11 Selectively Inhibits Aeroallergen-Induced Pulmonary Eosinophilia and Th2 Cytokine Production. J. Immunol. 165: 2222-2231 [Abstract] [Full Text]  
• LAMKHIOUED, B., GARCIA-ZEPEDA, E. A., ABI-YOUNES, S., NAKAMURA, H., JEDRZKIEWICZ, S., WAGNER, L., RENZI, P. M., ALLAKHVERDI, Z., LILLY, C., HAMID, Q., LUSTER, A. D. (2000). Monocyte Chemoattractant Protein (MCP)-4 Expression in the Airways of Patients with Asthma . Induction in Epithelial Cells and Mononuclear Cells by Proinflammatory Cytokines. Am. J. Respir. Crit. Care Med. 162: 723-732 [Abstract] [Full Text]  
• Webb, D. C., McKenzie, A. N. J., Koskinen, A. M. L., Yang, M., Mattes, J., Foster, P. S. (2000). Integrated Signals Between IL-13, IL-4, and IL-5 Regulate Airways Hyperreactivity. J. Immunol. 165: 108-113 [Abstract] [Full Text]  
• Wills-Karp, M. (2000). Trophic Slime, Allergic Slime. Am. J. Respir. Cell Mol. Bio. 22: 637-639 [Full Text]  
• KNOTT, P. G., GATER, P. R., BERTRAND, C. P. (2000). Airway Inflammation Driven by Antigen-specific Resident Lung CD4+ T Cells in alpha beta -T Cell Receptor Transgenic Mice. Am. J. Respir. Crit. Care Med. 161: 1340-1348 [Abstract] [Full Text]  
• Zuhdi Alimam, M., Piazza, F. M., Selby, D. M., Letwin, N., Huang, L., Rose, M. C. (2000). Muc-5/5ac Mucin Messenger RNA and Protein Expression Is a Marker of Goblet Cell Metaplasia in Murine Airways. Am. J. Respir. Cell Mol. Bio. 22: 253-260 [Abstract] [Full Text]  

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