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,
Center for Immunology and Departments of
*
Internal Medicine and
Pathology and
Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110
Although evidence is strong that Th cells play a major role in mediating the airway inflammation observed in asthma, the relative contributions of the Th cell subsets, Th1 and Th2, are unclear. It has been suggested that asthma is driven by Th2 predominant responses in the lung, but other data suggest a role for Th1 cells as well. Here we show by intracellular cytokine staining and flow cytometric analysis that in the murine model of OVA-induced airway inflammation, both Th1 and Th2 cells are recruited to the airways. Th1 cells predominate early in the response and Th2 cells predominate late. We further show that increasing the number of Th1 cells by passive transfer of OVA-specific Th1 cells results in increased inflammation. This effect is observed regardless of whether the T cells are transferred before sensitization or after airway inflammation is already in progress. Transfer of Th1 cells also results in increased recruitment of host T cells of both Th1 and Th2 phenotypes. Passive transfer of Th2 cells results in little change in the inflammatory response. These results demonstrate that Ag-specific Th1 cells are not protective in this model of asthma, but rather may potentiate the inflammatory response.
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 A Fukushima, K Fukata, A Ozaki, M Takata, N Kuroda, H Enzan, and H Ueno Exertion of the suppressive effects of IFN-{gamma} on experimental immune mediated blepharoconjunctivitis in Brown Norway rats during the induction phase but not the effector phase Br J Ophthalmol, October 1, 2002; 86(10): 1166 - 1171. [Abstract] [Full Text] [PDF]
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B. D. Medoff, A. Sauty, A. M. Tager, J. A. Maclean, R. N. Smith, A. Mathew, J. H. Dufour, and A. D. Luster IFN-{gamma}-Inducible Protein 10 (CXCL10) Contributes to Airway Hyperreactivity and Airway Inflammation in a Mouse Model of Asthma J. Immunol., May 15, 2002; 168(10): 5278 - 5286. [Abstract] [Full Text] [PDF]
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H. P. Jones, L. Tabor, X. Sun, M. D. Woolard, and J. W. Simecka Depletion of CD8+ T Cells Exacerbates CD4+ Th Cell-Associated Inflammatory Lesions During Murine Mycoplasma Respiratory Disease J. Immunol., April 1, 2002; 168(7): 3493 - 3501. [Abstract] [Full Text] [PDF]
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N. W. Lukacs, A. Berlin, D. Schols, R. T. Skerlj, and G. J. Bridger AMD3100, a CxCR4 Antagonist, Attenuates Allergic Lung Inflammation and Airway Hyperreactivity Am. J. Pathol., April 1, 2002; 160(4): 1353 - 1360. [Abstract] [Full Text] [PDF]
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H. Akiba, J. Kehren, M.-T. Ducluzeau, M. Krasteva, F. Horand, D. Kaiserlian, F. Kaneko, and J.-F. Nicolas Skin Inflammation During Contact Hypersensitivity Is Mediated by Early Recruitment of CD8+ T Cytotoxic 1 Cells Inducing Keratinocyte Apoptosis J. Immunol., March 15, 2002; 168(6): 3079 - 3087. [Abstract] [Full Text] [PDF]
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J. W. Verbsky, D. A. Randolph, L. P. Shornick, and D. D. Chaplin Nonhematopoietic Expression of Janus Kinase 3 Is Required for Efficient Recruitment of Th2 Lymphocytes and Eosinophils in OVA-Induced Airway Inflammation J. Immunol., March 1, 2002; 168(5): 2475 - 2482. [Abstract] [Full Text] [PDF]
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C. A. Byersdorfer and D. D. Chaplin Visualization of Early APC/T Cell Interactions in the Mouse Lung Following Intranasal Challenge J. Immunol., December 15, 2001; 167(12): 6756 - 6764. [Abstract] [Full Text] [PDF]
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 J. Liu, B. E. Anderson, M. E. Robert, J. M. McNiff, S. G. Emerson, W. D. Shlomchik, and M. J. Shlomchik Selective T-cell subset ablation demonstrates a role for T1 and T2 cells in ongoing acute graft-versus-host disease: a model system for the reversal of disease Blood, December 1, 2001; 98(12): 3367 - 3375. [Abstract] [Full Text] [PDF]
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S. S. SALVI, K. SURESH BABU, and S. T. HOLGATE Is Asthma Really Due to a Polarized T Cell Response Toward a Helper T Cell Type 2 Phenotype? Am. J. Respir. Crit. Care Med., October 15, 2001; 164(8): 1343 - 1346. [Full Text] [PDF]
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H. P. Jones, L. M. Hodge, K. Fujihashi, H. Kiyono, J. R. McGhee, and J. W. Simecka The Pulmonary Environment Promotes Th2 Cell Responses After Nasal-Pulmonary Immunization with Antigen Alone, but Th1 Responses Are Induced During Instances of Intense Immune Stimulation J. Immunol., October 15, 2001; 167(8): 4518 - 4526. [Abstract] [Full Text] [PDF]
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D. D'AMBROSIO, M. MARIANI, P. PANINA-BORDIGNON, and F. SINIGAGLIA Chemokines and Their Receptors Guiding T Lymphocyte Recruitment in Lung Inflammation Am. J. Respir. Crit. Care Med., October 1, 2001; 164(7): 1266 - 1275. [Full Text] [PDF]
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A. Takaoka, Y. Tanaka, T. Tsuji, T. Jinushi, A. Hoshino, Y. Asakura, Y. Mita, K. Watanabe, S. Nakaike, Y. Togashi, et al. A Critical Role for Mouse CXC Chemokine(s) in Pulmonary Neutrophilia During Th Type 1-Dependent Airway Inflammation J. Immunol., August 15, 2001; 167(4): 2349 - 2353. [Abstract] [Full Text] [PDF]
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D. M. Walter, C. P. Wong, R. H. DeKruyff, G. J. Berry, S. Levy, and D. T. Umetsu IL-18 Gene Transfer by Adenovirus Prevents the Development of and Reverses Established Allergen-Induced Airway Hyperreactivity J. Immunol., May 15, 2001; 166(10): 6392 - 6398. [Abstract] [Full Text] [PDF]
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 L. M. Hodge, M. Marinaro, H. P. Jones, J. R. McGhee, H. Kiyono, and J. W. Simecka Immunoglobulin A (IgA) Responses and IgE-Associated Inflammation along the Respiratory Tract after Mucosal but Not Systemic Immunization Infect. Immun., April 1, 2001; 69(4): 2328 - 2338. [Abstract] [Full Text] [PDF]
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J.C. Kips, K.G. Tournoy, and R.A. Pauwels New anti-asthma therapies: suppression of the effect of interleukin (IL)-4 and IL-5 Eur. Respir. J., March 1, 2001; 17(3): 499 - 506. [Abstract] [Full Text] [PDF]
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S.-s. J. Sung, C. E. Rose Jr., and S. M. Fu Intratracheal Priming with Ovalbumin- and Ovalbumin 323-339 Peptide-Pulsed Dendritic Cells Induces Airway Hyperresponsiveness, Lung Eosinophilia, Goblet Cell Hyperplasia, and Inflammation J. Immunol., January 15, 2001; 166(2): 1261 - 1271. [Abstract] [Full Text] [PDF]
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Z. Peng, H. Wang, X. Mao, K. T. HayGlass, and F. E. R. Simons CpG oligodeoxynucleotide vaccination suppresses IgE induction but may fail to down-regulate ongoing IgE responses in mice Int. Immunol., January 1, 2001; 13(1): 3 - 11. [Abstract] [Full Text] [PDF]
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T.-J. Huang, P. A. MacAry, P. Eynott, A. Moussavi, K. C. Daniel, P. W. Askenase, D. M. Kemeny, and K. F. Chung Allergen-Specific Th1 Cells Counteract Efferent Th2 Cell-Dependent Bronchial Hyperresponsiveness and Eosinophilic Inflammation Partly Via IFN-{{gamma}} J. Immunol., January 1, 2001; 166(1): 207 - 217. [Abstract] [Full Text] [PDF]
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D. C. Tsitoura, S. Kim, K. Dabbagh, G. Berry, D. B. Lewis, and D. T. Umetsu Respiratory Infection with Influenza A Virus Interferes with the Induction of Tolerance to Aeroallergens J. Immunol., September 15, 2000; 165(6): 3484 - 3491. [Abstract] [Full Text] [PDF]
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C. A. JONES and P. G. HOLT Immunopathology of Allergy and Asthma in Childhood Am. J. Respir. Crit. Care Med., August 1, 2000; 162(2): S36 - 39. [Full Text] [PDF]
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P. G. KNOTT, P. R. GATER, and C. P. BERTRAND 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., April 1, 2000; 161(4): 1340 - 1348. [Abstract] [Full Text]
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M. Castro, D. D. Chaplin, M. J. Walter, and M. J. Holtzman Could Asthma Be Worsened by Stimulating the T-helper Type 1 Immune Response? Am. J. Respir. Cell Mol. Biol., February 1, 2000; 22(2): 143 - 146. [Full Text]
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 D. A. Randolph, G. Huang, C. J. Carruthers, L. E. Bromley, and D. D. Chaplin The Role of CCR7 in TH1 and TH2 Cell Localization and Delivery of B Cell Help in Vivo Science, December 10, 1999; 286(5447): 2159 - 2162. [Abstract] [Full Text]
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D. T. Umetsu and R. H. DeKruyff Interleukin-10 . The Missing Link in Asthma Regulation? Am. J. Respir. Cell Mol. Biol., November 1, 1999; 21(5): 562 - 563. [Full Text]
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L. Cohn, R. J. Homer, N. Niu, and K. Bottomly T Helper 1 Cells and Interferon {gamma} Regulate Allergic Airway Inflammation and Mucus Production J. Exp. Med., November 1, 1999; 190(9): 1309 - 1318. [Abstract] [Full Text] [PDF]
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