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The Journal of Immunology, Vol 150, Issue 3 771-781, Copyright © 1993 by American Association of Immunologists
ARTICLES |
KE Pollok, YJ Kim, Z Zhou, J Hurtado, KK Kim, RT Pickard and BS Kwon
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis 46202.
4-1BB is an inducible receptor-like protein expressed in both cytolytic and Th cells. Optimal induction of 4-1BB mRNA in T cells required both PMA and ionomycin stimulation, indicating that protein kinase C activation and increases in intracellular Ca2+ were required for its expression. 4-1BB was categorized as an early activation gene since the protein synthesis inhibitor, cycloheximide, blocked the induction of 4- 1BB mRNA. A rat mAb, 53A2, was generated against recombinant soluble 4- 1BB and was used to characterize this molecule. 4-1BB is a 30-kDa glycoprotein and appears to exist as both a monomer and a 55-kDa dimer on the cell surface of a T cell clone. The 4-1BB protein may be post- translationally modified since its predicted backbone is 25 kDa. FACS analysis indicated that 4-1BB was inducible and expressed on the cell surface of activated splenic T cells and thymocytes. Cross-linking of 4- 1BB on anti-CD3-stimulated T cells with 53A2 resulted in a dramatic enhancement of T cell proliferation. This suggests that 4-1BB may function as an accessory signaling molecule during T cell activation.
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 A. Yamada, A. D. Salama, and M. H. Sayegh The Role of Novel T Cell Costimulatory Pathways in Autoimmunity and Transplantation J. Am. Soc. Nephrol., February 1, 2002; 13(2): 559 - 575. [Full Text] [PDF]
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Y. Sun, X. Lin, H. M. Chen, Q. Wu, S. K. Subudhi, L. Chen, and Y.-X. Fu Administration of Agonistic Anti-4-1BB Monoclonal Antibody Leads to the Amelioration of Experimental Autoimmune Encephalomyelitis J. Immunol., February 1, 2002; 168(3): 1457 - 1465. [Abstract] [Full Text] [PDF]
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J. L. Riley, P. J. Blair, J. T. Musser, R. Abe, K. Tezuka, T. Tsuji, and C. H. June ICOS Costimulation Requires IL-2 and Can Be Prevented by CTLA-4 Engagement J. Immunol., April 15, 2001; 166(8): 4943 - 4948. [Abstract] [Full Text] [PDF]
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J. A. Kim, B. J. Averbook, K. Chambers, K. Rothchild, J. Kjaergaard, R. Papay, and S. Shu Divergent Effects of 4-1BB Antibodies on Antitumor Immunity and on Tumor-reactive T-Cell Generation Cancer Res., March 1, 2001; 61(5): 2031 - 2037. [Abstract] [Full Text]
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B. R. Blazar, B. S. Kwon, A. Panoskaltsis-Mortari, K. B. Kwak, J. J. Peschon, and P. A. Taylor Ligation of 4-1BB (CDw137) Regulates Graft-Versus-Host Disease, Graft-Versus-Leukemia, and Graft Rejection in Allogeneic Bone Marrow Transplant Recipients J. Immunol., March 1, 2001; 166(5): 3174 - 3183. [Abstract] [Full Text] [PDF]
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 O. Martinet, V. Ermekova, J. Q. Qiao, B. Sauter, J. Mandeli, L. Chen, and S.-H. Chen Immunomodulatory Gene Therapy With Interleukin 12 and 4-1BB Ligand: Long- Term Remission of Liver Metastases in a Mouse Model J Natl Cancer Inst, June 7, 2000; 92(11): 931 - 936. [Abstract] [Full Text] [PDF]
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J. T. Tan, J. K. Whitmire, K. Murali-Krishna, R. Ahmed, J. D. Altman, R. S. Mittler, A. Sette, T. C. Pearson, and C. P. Larsen 4-1BB Costimulation Is Required for Protective Anti-Viral Immunity After Peptide Vaccination J. Immunol., March 1, 2000; 164(5): 2320 - 2325. [Abstract] [Full Text] [PDF]
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G. Kienzle and J. von Kempis CD137 (ILA/4-1BB), expressed by primary human monocytes, induces monocyte activation and apoptosis of B lymphocytes Int. Immunol., January 1, 2000; 12(1): 73 - 82. [Abstract] [Full Text] [PDF]
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 R. S. Mittler, T. S. Bailey, K. Klussman, M. D. Trailsmith, and M. K. Hoffmann Anti-4-1BB Monoclonal Antibodies Abrogate T Cell-dependent Humoral Immune Responses In Vivo through the Induction of Helper T Cell Anergy J. Exp. Med., November 15, 1999; 190(10): 1535 - 1540. [Abstract] [Full Text] [PDF]
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M. A. DeBenedette, T. Wen, M. F. Bachmann, P. S. Ohashi, B. H. Barber, K. L. Stocking, J. J. Peschon, and T. H. Watts Analysis of 4-1BB Ligand (4-1BBL)-Deficient Mice and of Mice Lacking Both 4-1BBL and CD28 Reveals a Role for 4-1BBL in Skin Allograft Rejection and in the Cytotoxic T Cell Response to Influenza Virus J. Immunol., November 1, 1999; 163(9): 4833 - 4841. [Abstract] [Full Text] [PDF]
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J. T. Tan, J. K. Whitmire, R. Ahmed, T. C. Pearson, and C. P. Larsen 4-1BB Ligand, a Member of the TNF Family, Is Important for the Generation of Antiviral CD8 T Cell Responses J. Immunol., November 1, 1999; 163(9): 4859 - 4868. [Abstract] [Full Text] [PDF]
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 J. Langstein, J. Michel, and H. Schwarz CD137 Induces Proliferation and Endomitosis in Monocytes Blood, November 1, 1999; 94(9): 3161 - 3168. [Abstract] [Full Text] [PDF]
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J. L. Cannons, K. P. Hoeflich, J. R. Woodgett, and T. H. Watts Role of the Stress Kinase Pathway in Signaling Via the T Cell Costimulatory Receptor 4-1BB J. Immunol., September 15, 1999; 163(6): 2990 - 2998. [Abstract] [Full Text] [PDF]
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H. Sepulveda, A. Cerwenka, T. Morgan, and R. W. Dutton CD28, IL-2-Independent Costimulatory Pathways for CD8 T Lymphocyte Activation J. Immunol., August 1, 1999; 163(3): 1133 - 1142. [Abstract] [Full Text] [PDF]
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D. M. Fernandes, A. M. Baird, L. J. Berg, and K. L. Rock A Monoclonal Antibody Reactive with a 40-kDa Molecule on Fetal Thymocytes and Tumor Cells Blocks Proliferation and Stimulates Aggregation and Apoptosis J. Immunol., August 1, 1999; 163(3): 1306 - 1314. [Abstract] [Full Text] [PDF]
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H. GUDMUNDSDOTTIR and L. A. TURKA T Cell Costimulatory Blockade: New Therapies for TransplantRejection J. Am. Soc. Nephrol., June 1, 1999; 10(6): 1356 - 1365. [Abstract] [Full Text]
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B.-a. Guinn, M. A. DeBenedette, T. H. Watts, and N. L. Berinstein 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., April 15, 1999; 162(8): 5003 - 5010. [Abstract] [Full Text] [PDF]
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B. Kwon, K.-Y. Yu, J. Ni, G.-L. Yu, I.-K. Jang, Y.-J. Kim, L. Xing, D. Liu, S.-X. Wang, and B. S. Kwon Identification of a Novel Activation-inducible Protein of the Tumor Necrosis Factor Receptor Superfamily and Its Ligand J. Biol. Chem., March 5, 1999; 274(10): 6056 - 6061. [Abstract] [Full Text] [PDF]
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J. A. Harrop, P. C. McDonnell, M. Brigham-Burke, S. D. Lyn, J. Minton, K. B. Tan, K. Dede, J. Spampanato, C. Silverman, P. Hensley, et al. Herpesvirus Entry Mediator Ligand (HVEM-L), a Novel Ligand for HVEM/TR2, Stimulates Proliferation of T Cells and Inhibits HT29 Cell Growth J. Biol. Chem., October 16, 1998; 273(42): 27548 - 27556. [Abstract] [Full Text] [PDF]
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 B. S. Kwon, S. Wang, N. Udagawa, V. Haridas, Z. H. Lee, K. K. Kim, K.-o. Oh, J. Greene, Y. Li, J. Su, et al. TR1, a new member of the tumor necrosis factor receptor superfamily, induces fibroblast proliferation and inhibits osteoclastogenesis and bone resorption FASEB J, July 1, 1998; 12(10): 845 - 854. [Abstract] [Full Text]
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K. Saoulli, S. Y. Lee, J. L. Cannons, W. C. Yeh, A. Santana, M. D. Goldstein, N. Bangia, M. A. DeBenedette, T. W. Mak, Y. Choi, et al. CD28-independent, TRAF2-dependent Costimulation of Resting T Cells by 4-1BB Ligand J. Exp. Med., June 1, 1998; 187(11): 1849 - 1862. [Abstract] [Full Text] [PDF]
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J. Langstein, J. Michel, J. Fritsche, M. Kreutz, R. Andreesen, and H. Schwarz CD137 (ILA/4-1BB), a Member of the TNF Receptor Family, Induces Monocyte Activation via Bidirectional Signaling J. Immunol., March 1, 1998; 160(5): 2488 - 2494. [Abstract] [Full Text] [PDF]
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J. N. Agrewala, S. Suvas, R. K. Verma, and G. C. Mishra Differential Effect of Anti-B7-1 and Anti-M150 Antibodies in Restricting the Delivery of Costimulatory Signals from B Cells and Macrophages J. Immunol., February 1, 1998; 160(3): 1067 - 1077. [Abstract] [Full Text] [PDF]
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D. N.J. Hart Dendritic Cells: Unique Leukocyte Populations Which Control the Primary Immune Response Blood, November 1, 1997; 90(9): 3245 - 3287. [Full Text] [PDF]
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W. W. Shuford, K. Klussman, D. D. Tritchler, D. T. Loo, J. Chalupny, A. W. Siadak, T. J. Brown, J. Emswiler, H. Raecho, C. P. Larsen, et al. 4-1BB Costimulatory Signals Preferentially Induce CD8+ T Cell Proliferation and Lead to the Amplification In Vivo of Cytotoxic T Cell Responses J. Exp. Med., July 7, 1997; 186(1): 47 - 55. [Abstract] [Full Text] [PDF]
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B. S. Kwon, K. B. Tan, J. Ni, K. K. Kim, Y.-J. Kim, S. Wang, R. Gentz, G.-L. Yu, J. Harrop, S. D. Lyn, et al. A Newly Identified Member of the Tumor Necrosis Factor Receptor Superfamily with a Wide Tissue Distribution and Involvement in Lymphocyte Activation J. Biol. Chem., May 30, 1997; 272(22): 14272 - 14276. [Abstract] [Full Text] [PDF]
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D. T. Loo, N. J. Chalupny, J. Bajorath, W. W. Shuford, R. S. Mittler, and A. Aruffo Analysis of 4-1BBL and Laminin Binding to Murine 4-1BB, a Member of the Tumor Necrosis Factor Receptor Superfamily, and Comparison with Human 4-1BB J. Biol. Chem., March 7, 1997; 272(10): 6448 - 6456. [Abstract] [Full Text] [PDF]
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