HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gajewska, B. U. Articles by Jordana, M. Search for Related Content PubMed PubMed Citation Articles by Gajewska, B. U. Articles by Jordana, M.

B7RP-1 Is Not Required for the Generation of Th2 Responses in a Model of Allergic Airway Inflammation but Is Essential for the Induction of Inhalation Tolerance¹

Beata U. Gajewska^*, Anna Tafuri, Filip K. wirski^*, Tina Walker^*, Jill R. Johnson^*, Theresa Shea^*, Arda Shahinian, Susanna Goncharova^*, Tak W. Mak, Martin R. Stämpfli^* and Manel Jordana^2,*

^* Department of Pathology and Molecular Medicine, and Division of Respiratory Diseases and Allergy, Centre For Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada; and Ontario Cancer Institute, and Department of Medical Biophysics and Immunology, University of Toronto, Toronto, Ontario, Canada

The recently described ICOS-B7RP-1 costimulatory pathway has been implicated in the generation of effector Th2 responses and, hence, has become an attractive therapeutic target for allergic diseases. In the present study, we used B7RP-1-deficient mice to investigate the role of B7RP-1 in the generation and maintenance of Th2 responses in a model of mucosal allergic airway inflammation. We found that exposure of B7RP-1 knockout mice to aerosolized OVA in the context of GM-CSF leads to airway eosinophilic inflammation. This response was long lasting because rechallenge of mice with the same Ag recapitulated airway eosinophilia. Moreover, significant expression of T1/ST2 on T cells and production of Th2-affiliated cytokines (IL-5, IL-4, and IL-13) and Igs (IgE and IgG1) conclusively demonstrate the generation of a Th2 response in the absence of B7RP-1. In addition, expression of two major Th2-associated costimulatory molecules—CD28 and ICOS—indicates T cell activation in the absence of B7RP-1 signaling. Finally, B7RP-1 knockout mice are resistant to the induction of inhalation tolerance as indicated by the sustained eosinophilia in the lung and IL-5 production. In summary, our results demonstrate that in a model of mucosal allergic sensitization, the ICOS-B7RP-1 pathway is redundant for the generation of Th2 responses but essential for the induction of inhalation tolerance.

This article has been cited by other articles:

				Y. Burmeister, T. Lischke, A. C. Dahler, H. W. Mages, K.-P. Lam, A. J. Coyle, R. A. Kroczek, and A. Hutloff ICOS Controls the Pool Size of Effector-Memory and Regulatory T Cells J. Immunol., January 15, 2008; 180(2): 774 - 782. [Abstract] [Full Text] [PDF]

				A. Amatucci, T. Novobrantseva, K. Gilbride, M. Brickelmaier, P. Hochman, and A. Ibraghimov Recombinant ST2 boosts hepatic Th2 response in vivo J. Leukoc. Biol., July 1, 2007; 82(1): 124 - 132. [Abstract] [Full Text] [PDF]

				C. L. Van Hove, T. Maes, G. F. Joos, and K. G. Tournoy Prolonged Inhaled Allergen Exposure Can Induce Persistent Tolerance Am. J. Respir. Cell Mol. Biol., May 1, 2007; 36(5): 573 - 584. [Abstract] [Full Text] [PDF]

				E. H. Wilson, C. Zaph, M. Mohrs, A. Welcher, J. Siu, D. Artis, and C. A. Hunter B7RP-1-ICOS Interactions Are Required for Optimal Infection-Induced Expansion of CD4+ Th1 and Th2 Responses J. Immunol., August 15, 2006; 177(4): 2365 - 2372. [Abstract] [Full Text] [PDF]

				K. Vermaelen and R. Pauwels Pulmonary Dendritic Cells Am. J. Respir. Crit. Care Med., September 1, 2005; 172(5): 530 - 551. [Abstract] [Full Text] [PDF]