Journal of Experimental Medicine, Vol 180, 631-640, Copyright © 1994 by Rockefeller University Press

ARTICLES

Comparative analysis of B7-1 and B7-2 costimulatory ligands: expression and function

KS Hathcock, G Laszlo, C Pucillo, P Linsley and RJ Hodes
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.

Antigen-specific T cell activation requires the engagement of the T cell receptor (TCR) with antigen as well as the engagement of appropriate costimulatory molecules. The most extensively characterized pathway of costimulation has been that involving the interaction of CD28 and CTLA4 on the T cell with B7 (now termed B7-1) on antigen presenting cells. Recently, B7-2 a second costimulatory ligand for CTLA4, was described, demonstrating the potential complexity of costimulatory interactions. This report examines and compares the expression and function of B7-1 and B7-2. Overall these results indicate that (a) B7-1 and B7-2 can be expressed by multiple cell types, including B cells, T cells, macrophages, and dendritic cells, all of which are therefore candidate populations for delivering costimulatory signals mediated by these molecules; (b) stimulating B cells with either LPS or anti-IgD-dextran induced expression of both B7- 1 and B7-2, and peak expression of both costimulatory molecules occurred after 18-42 h of culture. Expression of B7-2 on these B cell populations was significantly higher than expression of B7-1 at all times assayed after stimulation; (c) blocking of B7-2 costimulatory activity inhibited TCR-dependent T cell proliferation and cytokine production, without affecting early consequences of TCR signaling such as induction of CD69 or interleukin 2 receptor alpha (IL-2R alpha); and (d) expression of B7-1 and of B7-2 can be regulated by a variety of stimuli. Moreover, expression of B7-1 and B7-2 can be independently regulated by the same stimulus, providing an additional complexity in the mechanisms available for regulating costimulation and hence immune response.
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• Cho, S. K., Webber, T. D., Carlyle, J. R., Nakano, T., Lewis, S. M., Zuniga-Pflucker, J. C. (1999). Functional characterization of B lymphocytes generated in vitro from embryonic stem cells. Proc. Natl. Acad. Sci. USA 96: 9797-9802 [Abstract] [Full Text]  
• Woerly, G., Roger, N., Loiseau, S., Dombrowicz, D., Capron, A., Capron, M. (1999). Expression of CD28 and CD86 by Human Eosinophils and Role in the Secretion of Type 1 Cytokines (Interleukin 2 and Interferon {gamma}): Inhibition by Immunoglobulin A Complexes. JEM 190: 487-496 [Abstract] [Full Text]  
• Agostini, C., Trentin, L., Perin, A., Facco, M., Siviero, M., Piazza, F., Basso, U., Adami, F., Zambello, R., Semenzato, G. (1999). Regulation of alveolar macrophage-T cell interactions during Th1-type sarcoid inflammatory process. Am. J. Physiol. Lung Cell. Mol. Physiol. 277: L240-L250 [Abstract] [Full Text]  
• Perrin, P. J., June, C. H., Maldonado, J. H., Ratts, R. B., Racke, M. K. (1999). Blockade of CD28 During In Vitro Activation of Encephalitogenic T Cells or After Disease Onset Ameliorates Experimental Autoimmune Encephalomyelitis. J. Immunol. 163: 1704-1710 [Abstract] [Full Text]  
• Akiba, H., Oshima, H., Takeda, K., Atsuta, M., Nakano, H., Nakajima, A., Nohara, C., Yagita, H., Okumura, K. (1999). CD28-Independent Costimulation of T Cells by OX40 Ligand and CD70 on Activated B Cells. J. Immunol. 162: 7058-7066 [Abstract] [Full Text]  
• Oliver, A. M., Martin, F., Kearney, J. F. (1999). IgMhighCD21high Lymphocytes Enriched in the Splenic Marginal Zone Generate Effector Cells More Rapidly Than the Bulk of Follicular B Cells. J. Immunol. 162: 7198-7207 [Abstract] [Full Text]  
• ISRAËL-ASSAYAG, E., DAKHAMA, A., LAVIGNE, S., LAVIOLETTE, M., CORMIER, Y. (1999). Expression of Costimulatory Molecules on Alveolar Macrophages in Hypersensitivity Pneumonitis. Am. J. Respir. Crit. Care Med. 159: 1830-1834 [Abstract] [Full Text]  
• Elloso, M. M., Scott, P. (1999). Expression and Contribution of B7-1 (CD80) and B7-2 (CD86) in the Early Immune Response to Leishmania major Infection. J. Immunol. 162: 6708-6715 [Abstract] [Full Text]  
• Guinn, B.-a., DeBenedette, M. A., Watts, T. H., Berinstein, N. L. (1999). 4-1BBL Cooperates with B7-1 and B7-2 in Converting a B Cell Lymphoma Cell Line into a Long-Lasting Antitumor Vaccine. J. Immunol. 162: 5003-5010 [Abstract] [Full Text]  
• Greenwald, R. J., Urban, J. F., Ekkens, M. J., Chen, S.-J., Nguyen, D., Fang, H., Finkelman, F. D., Sharpe, A. H., Gause, W. C. (1999). B7-2 Is Required for the Progression But Not the Initiation of the Type 2 Immune Response to a Gastrointestinal Nematode Parasite. J. Immunol. 162: 4133-4139 [Abstract] [Full Text]  
• Stremmel, C., Greenfield, E.A., Howard, E., Freeman, G.J., Kuchroo, V.K. (1999). B7-2 Expressed on EL4 Lymphoma Suppresses Antitumor Immunity by an Interleukin 4-dependent Mechanism. JEM 189: 919-930 [Abstract] [Full Text]  
• Tanaka, H., Yoshizawa, H., Yamaguchi, Y., Ito, K., Kagamu, H., Suzuki, E., Gejyo, F., Hamada, H., Arakawa, M. (1999). Successful Adoptive Immunotherapy of Murine Poorly Immunogenic Tumor with Specific Effector Cells Generated from Gene-Modified Tumor-Primed Lymph Node Cells. J. Immunol. 162: 3574-3582 [Abstract] [Full Text]  

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