J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/05/1671/10 $2.00
Volume 185, Number 9, May 5, 1997 1671-1680

Costimulation through B7-2 (CD86) Is Required for the Induction of a Lung Mucosal T Helper Cell 2 (TH2) Immune Response and Altered Airway Responsiveness

By Shogo Tsuyuki, Junko Tsuyuki,^* Karin Einsle,^* Manfred Kopf,^§ and Anthony J. Coyle^*

From ^* Ciba-Geigy Ltd., Asthma and Allergy Research Department, Pharmaceutical Division, CH-4002 Basel, Switzerland;  R&D Dept. Kissei Pharmaceutical Co. Ltd., Matsumoto, 399, Japan; ^§ Basel Institute for Immunology, CH-4005 Basel, Switzerland

The recruitment of eosinophils into the airways after allergen exposure is dependent on interleukin (IL) 5 secreted from antigen-specific CD4⁺ T cells of the T helper cell (Th) 2 subset. However, while it is established that costimulation through CD28 is required for TCR-mediated activation and IL-2 production, the importance of this mechanism for the induction of a Th2 immune response is less clear. In the present study, we administered the fusion protein CTLA-4 immunoglobulin (Ig) into the lungs before allergen provocation to determine whether CD28/CTLA-4 ligands are required for allergen-induced eosinophil accumulation and the production of Th2 cytokines. Administration of CTLA-4 Ig inhibited the recruitment of eosinophils into the lungs by 75% and suppressed IgE in the bronchoalveolar lavage fluid. CTLA-4 Ig also inhibited the production of IL-4, IL-5, and IL-10 by 70-80% and enhanced interferon- production from CD3-T cell receptor-activated lung Thy1.2+ cells. Allergen exposure upregulated expression of B7-2, but not B7-1, on B cells from the lung within 24 h. Moreover, airway administration of an anti-B7-2 monoclonal antibody (mAb) inhibited eosinophil infiltration, IgE production, and Th2 cytokine secretion comparable in magnitude to that observed with CTLA-4 Ig. Treatment with an anti-B7-1 mAb had a small, but significant effect on eosinophil accumulation, although was less effective in inhibiting Th2 cytokine production. The anti-B7-2, but not anti-B7-1, mAb also inhibited antigen-induced airway hyperresponsiveness in vivo. In all of the parameters assessed, the combination of both the anti-B7-1 and anti-B7-2 mAb was no more effective than anti-B7-2 mAb treatment alone. We propose that strategies aimed at inhibition of CD28 interactions with B7-2 molecules may represent a novel therapeutic target for the treatment of lung mucosal allergic inflammation.

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• Donovan, C. E., Mark, D. A., He, H. Z., Liou, H.-C., Kobzik, L., Wang, Y., De Sanctis, G. T., Perkins, D. L., Finn, P. W. (1999). NF-{kappa}B/Rel Transcription Factors: c-Rel Promotes Airway Hyperresponsiveness and Allergic Pulmonary Inflammation. J. Immunol. 163: 6827-6833 [Abstract] [Full Text]  
• Jaffar, Z. H., Stanciu, L., Pandit, A., Lordan, J., Holgate, S. T., Roberts, K. (1999). Essential Role for Both CD80 and CD86 Costimulation, But Not CD40 Interactions, in Allergen-Induced Th2 Cytokine Production from Asthmatic Bronchial Tissue: Role for {alpha}{beta}, But Not {gamma}{delta}, T Cells. J. Immunol. 163: 6283-6291 [Abstract] [Full Text]  
• Mathur, M., Herrmann, K., Qin, Y., Gulmen, F., Li, X., Krimins, R., Weinstock, J., Elliott, D., Bluestone, J. A., Padrid, P. (1999). CD28 Interactions with Either CD80 or CD86 Are Sufficient to Induce Allergic Airway Inflammation in Mice. Am. J. Respir. Cell Mol. Bio. 21: 498-509 [Abstract] [Full Text]  
• Tam, R. C., Lim, C., Bard, J., Pai, B. (1999). Contact Hypersensitivity Responses Following Ribavirin Treatment In Vivo Are Influenced by Type 1 Cytokine Polarization, Regulation of IL-10 Expression, and Costimulatory Signaling. J. Immunol. 163: 3709-3717 [Abstract] [Full Text]  
• Donovan, C. E, Finn, P. W (1999). Immune mechanisms of childhood asthma. Thorax 54: 938-946 [Full Text]  
• Tsitoura, D. C., DeKruyff, R. H., Lamb, J. R., Umetsu, D. T. (1999). Intranasal Exposure to Protein Antigen Induces Immunological Tolerance Mediated by Functionally Disabled CD4+ T Cells. J. Immunol. 163: 2592-2600 [Abstract] [Full Text]  
• van Neerven, R. J. J., Wikborg, T., Lund, G., Jacobsen, B., Brinch-Nielsen, A., Arnved, J., Ipsen, H. (1999). Blocking Antibodies Induced by Specific Allergy Vaccination Prevent the Activation of CD4+ T Cells by Inhibiting Serum-IgE-Facilitated Allergen Presentation. J. Immunol. 163: 2944-2952 [Abstract] [Full Text]  
• Soos, J. M., Ashley, T. A., Morrow, J., Patarroyo, J. C., Szente, B. E., Zamvil, S. S. (1999). Differential expression of B7 co-stimulatory molecules by astrocytes correlates with T cell activation and cytokine production. Int Immunol 11: 1169-1179 [Abstract] [Full Text]  
• Burastero, S. E, Rossi, G. A (1999). Immunomodulation by interference with co-stimulatory molecules: therapeutic perspectives in asthma. Thorax 54: 554-557 [Full Text]  
• Chabot, S., Williams, G., Hamilton, M., Sutherland, G., Yong, V. W. (1999). Mechanisms of IL-10 Production in Human Microglia-T Cell Interaction. J. Immunol. 162: 6819-6828 [Abstract] [Full Text]  
• HACZKU, A., TAKEDA, K., REDAI, I., HAMELMANN, E., CIESLEWICZ, G., JOETHAM, A., LOADER, J., LEE, J. J., IRVIN, C., GELFAND, E. W. (1999). Anti-CD86 (B7.2) Treatment Abolishes Allergic Airway Hyperresponsiveness in Mice. Am. J. Respir. Crit. Care Med. 159: 1638-1643 [Abstract] [Full Text]  
• Umland, S. P., Shah, H., Jakway, J. P., Shortall, J., Razac, S., Garlisi, C. G., Falcone, A., Kung, T. T., Stelts, D., Hegde, V., Patel, M., Motasim Billah, M., Egan, R. W. (1999). Effects of Cyclosporin A and Dinactin on T-Cell Proliferation, Interleukin-5 Production, and Murine Pulmonary Inflammation. Am. J. Respir. Cell Mol. Bio. 20: 481-492 [Abstract] [Full Text]  
• Korsgren, M., Persson, C. G.A., Sundler, F., Bjerke, T., Hansson, T., Chambers, B. J., Hong, S., Van Kaer, L., Ljunggren, H.-G., Korsgren, O. (1999). Natural Killer Cells Determine Development of Allergen-induced Eosinophilic Airway Inflammation in Mice. JEM 189: 553-562 [Abstract] [Full Text]  
• Larche, M., Till, S. J., Haselden, B. M., North, J., Barkans, J., Corrigan, C. J., Kay, A. B., Robinson, D. S. (1998). Costimulation Through CD86 Is Involved in Airway Antigen-Presenting Cell and T Cell Responses to Allergen in Atopic Asthmatics. J. Immunol. 161: 6375-6382 [Abstract] [Full Text]  
• Manickasingham, S. P., Anderton, S. M., Burkhart, C., Wraith, D. C. (1998). Qualitative and Quantitative Effects of CD28/B7-Mediated Costimulation on Naive T Cells In Vitro. J. Immunol. 161: 3827-3835 [Abstract] [Full Text]  
• Jirapongsananuruk, O., Hofer, M. F., Trumble, A. E., Norris, D. A., Leung, D. Y. M. (1998). Enhanced Expression of B7.2 (CD86) in Patients with Atopic Dermatitis: A Potential Role in the Modulation of IgE Synthesis. J. Immunol. 160: 4622-4627 [Abstract] [Full Text]  
• Lambrecht, B. N., Salomon, B., Klatzmann, D., Pauwels, R. A. (1998). Dendritic Cells Are Required for the Development of Chronic Eosinophilic Airway Inflammation in Response to Inhaled Antigen in Sensitized Mice. J. Immunol. 160: 4090-4097 [Abstract] [Full Text]  
• Keane-Myers, A. M., Gause, W. C., Finkelman, F. D., Xhou, X.-d., Wills-Karp, M. (1998). Development of Murine Allergic Asthma Is Dependent Upon B7-2 Costimulation. J. Immunol. 160: 1036-1043 [Abstract] [Full Text]  

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