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The Journal of Immunology, Vol 158, Issue 5 2042-2049, Copyright © 1997 by American Association of Immunologists
ARTICLES |
A Keane-Myers, WC Gause, PS Linsley, SJ Chen and M Wills-Karp
School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
We have previously demonstrated that the development of allergen- induced airway hyperresponsiveness in a murine model is CD4+ T cell dependent. In the present study, we examined the role of the B7/CD28- CTLA4 costimulatory T cell activation pathway in the pathogenesis of allergen-induced airway hyperresponsiveness in this murine model. Sensitized A/J mice develop significant increases in airway responsiveness, bronchoalveolar lavage eosinophils, serum IgE levels, and Th2-associated cytokine production following aspiration challenge with OVA. Administration of CTLA4-Ig either before Ag sensitization or before pulmonary Ag challenge abolished Ag-induced airway hyperresponsiveness and pulmonary eosinophilia. Examination of cytokine protein levels in the bronchoalveolar lavage showed a significant decrease in the level of the Th2 cytokine, IL-4, after CTLA4-Ig treatment either before sensitization or before challenge, with no significant change in the concentration of the Th1 cytokine, IFN-gamma. Further, the Ag-specific Ab isotypes IgG1 and IgE were significantly decreased in animals treated with CTLA4-Ig before challenge, while there was no significant change in the IgG2a Ab isotype. These data demonstrate that administration of CTLA4-Ig is effective in ablating allergen-induced airway dysfunction concomitant with a significant reduction in the Th2 response. We conclude that B7/CD28-CTLA-4 costimulation is required for the development of many of the immunologic and physiologic features of asthma, possibly by promoting a pathologic type 2-associated response.
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M. Larche, S. J. Till, B. M. Haselden, J. North, J. Barkans, C. J. Corrigan, A. B. Kay, and D. S. Robinson Costimulation Through CD86 Is Involved in Airway Antigen-Presenting Cell and T Cell Responses to Allergen in Atopic Asthmatics J. Immunol., December 1, 1998; 161(11): 6375 - 6382. [Abstract] [Full Text] [PDF]
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B. N. Lambrecht, B. Salomon, D. Klatzmann, and R. A. Pauwels Dendritic Cells Are Required for the Development of Chronic Eosinophilic Airway Inflammation in Response to Inhaled Antigen in Sensitized Mice J. Immunol., April 15, 1998; 160(8): 4090 - 4097. [Abstract] [Full Text] [PDF]
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M. WILLS-KARP and S. L. EWART The Genetics of Allergen-Induced Airway Hyperresponsiveness in Mice Am. J. Respir. Crit. Care Med., October 1, 1997; 156(4): S89 - S96. [Abstract] [Full Text] [PDF]
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M. Dupuis and D. M. McDonald Dendritic-cell Regulation of Lung Immunity Am. J. Respir. Cell Mol. Biol., September 1, 1997; 17(3): 284 - 286. [Full Text]
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