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Science 26 August 1994:
Vol. 265. no. 5176, pp. 1225 - 1227
DOI: 10.1126/science.7520604

Articles

Science, Vol 265, Issue 5176, 1225-1227
Copyright © 1994 by American Association for the Advancement of Science


articles

Treatment of murine lupus with CTLA4Ig

BK Finck, PS Linsley, and D Wofsy

Department of Medicine, University of California, San Francisco.

The interaction of B7-related molecules on antigen-presenting cells with CD28 or CTLA-4 antigens on T cells provides a second signal for T cell activation. Selection inhibition of the B7-CD28 or B7-CTLA-4 interactions produces antigen-specific T cell unresponsiveness in vitro and suppresses immune function in vivo. To determine whether selective inhibition of the B7-CD28 or B7-CTLA-4 interactions could suppress spontaneous autoimmune disease, a B7-binding protein was generated by genetic fusion of the extracellular domain of murine CTLA-4 to the Fc portion of a mouse immunoglobulin G2a monoclonal antibody (muCTLA4Ig). In lupus-prone NZB/NZW filial generation (F1) mice, treatment with muCTLA4Ig blocked autoantibody production and prolonged life, even when treatment was delayed until the most advanced stage of clinical illness. These findings suggest a possible role for human CTLA4Ig in the treatment of autoimmune diseases in humans.


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J. Immunol. 162, 1818-1826
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J. Immunol. 162, 1859-1867
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CD28-Deficient Mice Are Highly Resistant to Collagen-Induced Arthritis.
Y. Tada, K. Nagasawa, A. Ho, F. Morito, O. Ushiyama, N. Suzuki, H. Ohta, and T. W. Mak (1999)
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C. Conde, S. Weller, S. Gilfillan, L. Marcellin, T. Martin, and J.-L. Pasquali (1998)
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A. N. Schweitzer and A. H. Sharpe (1998)
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E.-N. Malvey, M. K. Jenkins, and D. L. Mueller (1998)
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K. Schlienger, K. Uyemura, D. Jullien, P. A. Sieling, T. H. Rea, P. S. Linsley3, and R. L. Modlin (1998)
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Tissue-Specific Up-Regulation of B7-1 Expression and Function During the Course of Murine Relapsing Experimental Autoimmune Encephalomyelitis.
N. J. Karandikar, C. L. Vanderlugt, T. Eagar, L. Tan, J. A. Bluestone, and S. D. Miller (1998)
J. Immunol. 161, 192-199
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Antibodies to DNA.
B. H. Hahn (1998)
N. Engl. J. Med. 338, 1359-1368
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Involvement of CD40 Ligand-CD40 and CTLA4-B7 Pathways in Murine Acute Graft-Versus-Host Disease Induced by Allogeneic T Cells Lacking CD28.
K. Saito, J. Sakurai, J. Ohata, T. Kohsaka, H. Hashimoto, K. Okumura, R. Abe, and M. Azuma (1998)
J. Immunol. 160, 4225-4231
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CTLA4Ig Inhibits Airway Eosinophilia and Hyperresponsiveness by Regulating the Development of Th1/Th2 Subsets in a Murine Model of Asthma.
P. A. Padrid, M. Mathur, X. Li, K. Herrmann, Y. Qin, A. Cattamanchi, J. Weinstock, D. Elliott, A. I. Sperling, and J. A. Bluestone (1998)
Am. J. Respir. Cell Mol. Biol. 18, 453-462
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Gene therapy in autoimmune diseases.
C H EVANS, J D WHALEN, C H EVANS, S C GHIVIZZANI, and P D ROBBINS (1998)
Ann Rheum Dis 57, 125-127
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Uncoupling of Immune Complex Formation and Kidney Damage in Autoimmune Glomerulonephritis.
R. Clynes, C. Dumitru, and J. V. Ravetch (1998)
Science 279, 1052-1054
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Development of Murine Allergic Asthma Is Dependent Upon B7-2 Costimulation.
A. M. Keane-Myers, W. C. Gause, F. D. Finkelman, X.-d. Xhou, and M. Wills-Karp (1998)
J. Immunol. 160, 1036-1043
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Modulation of Murine Lyme Borreliosis by Interruption of the B7/CD28 T-Cell Costimulatory Pathway.
M.-C. Shanafelt, I. Kang, S. W. Barthold, and L. K. Bockenstedt (1998)
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Immunologic Aspects of Renal Disease.
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CD80 Costimulation Is Essential for the Induction of Airway Eosinophilia.
N. Harris, R. Peach, J. Naemura, P. S. Linsley, G. Le Gros, and F. Ronchese (1997)
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Animal models of cutaneous lupus erythematosus and lupus erythematosus photosensitivity.
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Costimulatory B7 Molecules in the Pathogenesis of Infectious and Autoimmune Diseases.
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