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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Linhart, B. Articles by Wekerle, T. Search for Related Content PubMed PubMed Citation Articles by Linhart, B. Articles by Wekerle, T.

Costimulation Blockade Inhibits Allergic Sensitization but Does Not Affect Established Allergy in a Murine Model of Grass Pollen Allergy¹

Birgit Linhart^*, Sinda Bigenzahn, Arnulf Hartl, Christian Lupinek^*, Josef Thalhamer, Rudolf Valenta^2,* and Thomas Wekerle^2,3,*,

^* Christian Doppler Laboratory for Allergy Research, Division of Immunopathology, Department of Pathophysiology, Center of Physiology and Pathophysiology and Division of Transplantation, Department of Surgery, Medical University of Vienna, Austria; Department of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria; and Department of Molecular Biology, University of Salzburg, Salzburg, Austria

Type I allergy is characterized by the development of an initial Th2-dependent allergen-specific IgE response, which is boosted upon a subsequent allergen encounter. Although the immediate symptoms of allergy are mainly IgE-mediated, allergen-specific T cell responses contribute to the late phase as well as to the chronic manifestations of allergy. This study investigates the potential of costimulation blockade with CTLA4Ig and an anti-CD154 mAb for modifying the allergic immune response to the major timothy grass pollen allergen Phl p 5 in a mouse model. BALB/c mice were treated with the costimulation blockers at the time of primary sensitization to the Phl p 5 allergen or at the time of a secondary allergen challenge. Costimulation blockade (CTLA4Ig plus anti-CD154 or anti-CD154 alone) at the time of sensitization prevented the development of allergen-specific IgE, IgM, IgG, and IgA responses compared with untreated but sensitized mice. However, costimulation blockade had no influence on established IgE responses in sensitized mice. Immediate-type reactions as analyzed by a rat basophil leukemia cell mediator release assay were only suppressed by early treatment but not by a costimulation blockade after sensitization. CTLA4Ig given alone failed to suppress both the primary and the secondary allergen-specific Ab responses. Allergen-specific T cell activation was suppressed in mice by early as well as by a late costimulation blockade, suggesting that IgE responses in sensitized mice are independent of T cell help. Our results indicate that T cell suppression alone without active immune regulation or a shifting of the Th2/Th1 balance is not sufficient for the treatment of established IgE responses in an allergy.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This study was supported by Austrian Research Promotion Agency (Forschungsförderungsgesellschaft) Bridge Grant 810105-SCK/SAI, Christian Doppler Research Association (to R.V.) and Austrian Science Fund Grants SFB F2310-B13 (to T.W.), F1815 (to R.V.), and S8811 (to J.T.).

² R.V. and T.W. are cosenior authors of this article.

³ Address correspondence and reprint requests to Dr. Thomas Wekerle, Medical University of Vienna, Division of Transplantation, Department of Surgery, Vienna General Hospital, Waehringer Guertel 18-20, A-1090 Vienna, Austria. E-mail address: thomas.wekerle{at}meduniwien.ac.at

⁴ Abbreviations used in this paper: SI, stimulation index; RBL, rat basophil leukemia.

This article has been cited by other articles:

				U. Baranyi, B. Linhart, N. Pilat, M. Gattringer, J. Bagley, F. Muehlbacher, J. Iacomini, R. Valenta, and T. Wekerle Tolerization of a Type I Allergic Immune Response through Transplantation of Genetically Modified Hematopoietic Stem Cells J. Immunol., June 15, 2008; 180(12): 8168 - 8175. [Abstract] [Full Text] [PDF]

				M. Suzuki, X. Zheng, X. Zhang, M. Li, C. Vladau, T. E. Ichim, H. Sun, L. R. Min, B. Garcia, and W.-P. Min Novel Vaccination for Allergy through Gene Silencing of CD40 Using Small Interfering RNA J. Immunol., June 15, 2008; 180(12): 8461 - 8469. [Abstract] [Full Text] [PDF]

				K. Westritschnig, B. Linhart, M. Focke-Tejkl, T. Pavkov, W. Keller, T. Ball, A. Mari, A. Hartl, A. Stocklinger, S. Scheiblhofer, et al. A Hypoallergenic Vaccine Obtained by Tail-to-Head Restructuring of Timothy Grass Pollen Profilin, Phl p 12, for the Treatment of Cross-Sensitization to Profilin J. Immunol., December 1, 2007; 179(11): 7624 - 7634. [Abstract] [Full Text] [PDF]