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CUTTING EDGE |
*
Department of Microbiology, Oregon State University, Corvallis OR 97331; and
Department of Immunology and Inflammation, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08540
After recognition of Ag/MHC and ligation of a costimulatory molecule, resting T cells will clonally expand and then delete to very low levels. Previously, it was shown that deletion can be prevented by coinjection of cytokines or proinflammatory agents such as adjuvants. Here, we demonstrate that ligation of 4-1BB blocks deletion of superantigen-activated T cells in the absence of adjuvant or additional cytokine treatment. Nearly 10 times as many staphylococcal enterotoxin A-specific T cells were detected in the spleens of mice injected 21 days previously with staphylococcal enterotoxin A and an agonist anti-4-1BB Ab compared with mice given staphylococcal enterotoxin A and a control IgG. Even though both CD4- and CD8-activated T cells expressed 4-1BB, a higher proportion of CD8 T cells were rescued compared CD4 T cells. These data suggest that although 4-1BB provides costimulation, it may also promote long-term T cell survival.
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G. Rajagopalan, Y. C. Kudva, L. Chen, L. Wen, and C. S. David Autoimmune diabetes in HLA-DR3/DQ8 transgenic mice expressing the co-stimulatory molecule B7-1 in the {beta} cells of islets of Langerhans Int. Immunol., September 1, 2003; 15(9): 1035 - 1044. [Abstract] [Full Text] [PDF]
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Q. Li, A. Carr, F. Ito, S. Teitz-Tennenbaum, and A. E. Chang Polarization Effects of 4-1BB during CD28 Costimulation in Generating Tumor-reactive T Cells for Cancer Immunotherapy Cancer Res., May 15, 2003; 63(10): 2546 - 2552. [Abstract] [Full Text] [PDF]
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L. Myers, C. Takahashi, R. S. Mittler, R. J. Rossi, and A. T. Vella Effector CD8 T cells possess suppressor function after 4-1BB and Toll-like receptor triggering PNAS, April 29, 2003; 100(9): 5348 - 5353. [Abstract] [Full Text] [PDF]
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D. J. Shedlock, J. K. Whitmire, J. Tan, A. S. MacDonald, R. Ahmed, and H. Shen Role of CD4 T Cell Help and Costimulation in CD8 T Cell Responses During Listeria monocytogenes Infection J. Immunol., February 15, 2003; 170(4): 2053 - 2063. [Abstract] [Full Text] [PDF]
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J. W. Lillard Jr, U. P. Singh, P. N. Boyaka, S. Singh, D. D. Taub, and J. R. McGhee MIP-1alpha and MIP-1beta differentially mediate mucosal and systemic adaptive immunity Blood, February 1, 2003; 101(3): 807 - 814. [Abstract] [Full Text] [PDF]
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C. Berger, C. A. Blau, T. Clackson, S. R. Riddell, and S. Heimfeld CD28 costimulation and immunoaffinity-based selection efficiently generate primary gene-modified T cells for adoptive immunotherapy Blood, January 15, 2003; 101(2): 476 - 484. [Abstract] [Full Text] [PDF]
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H.-W. Lee, S.-J. Park, B. K. Choi, H. H. Kim, K.-O. Nam, and B. S. Kwon 4-1BB Promotes the Survival of CD8+ T Lymphocytes by Increasing Expression of Bcl-xL and Bfl-1 J. Immunol., November 1, 2002; 169(9): 4882 - 4888. [Abstract] [Full Text] [PDF]
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P. Bansal-Pakala and M. Croft Defective T Cell Priming Associated with Aging Can Be Rescued by Signaling Through 4-1BB (CD137) J. Immunol., November 1, 2002; 169(9): 5005 - 5009. [Abstract] [Full Text] [PDF]
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Y.-J. Kim, R. R. Brutkiewicz, and H. E. Broxmeyer Role of 4-1BB (CD137) in the functional activation of cord blood CD28-CD8+ T cells Blood, October 16, 2002; 100(9): 3253 - 3260. [Abstract] [Full Text] [PDF]
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S. Pauly, K. Broll, M. Wittmann, G. Giegerich, and H. Schwarz CD137 is expressed by follicular dendritic cells and costimulates B lymphocyte activation in germinal centers J. Leukoc. Biol., July 1, 2002; 72(1): 35 - 42. [Abstract] [Full Text] [PDF]
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T. Wen, J. Bukczynski, and T. H. Watts 4-1BB Ligand-Mediated Costimulation of Human T Cells Induces CD4 and CD8 T Cell Expansion, Cytokine Production, and the Development of Cytolytic Effector Function J. Immunol., May 15, 2002; 168(10): 4897 - 4906. [Abstract] [Full Text] [PDF]
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R. A. Wilcox, A. I. Chapoval, K. S. Gorski, M. Otsuji, T. Shin, D. B. Flies, K. Tamada, R. S. Mittler, H. Tsuchiya, D. M. Pardoll, et al. Expression of Functional CD137 Receptor by Dendritic Cells J. Immunol., May 1, 2002; 168(9): 4262 - 4267. [Abstract] [Full Text] [PDF]
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J. R. Maxwell, C. Ruby, N. I. Kerkvliet, and A. T. Vella Contrasting the Roles of Costimulation and the Natural Adjuvant Lipopolysaccharide During the Induction of T Cell Immunity J. Immunol., May 1, 2002; 168(9): 4372 - 4381. [Abstract] [Full Text] [PDF]
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G. Demirci, W. Gao, X. X. Zheng, T. R. Malek, T. B. Strom, and X. C. Li On CD28/CD40 Ligand Costimulation, Common {gamma}-Chain Signals, and the Alloimmune Response J. Immunol., May 1, 2002; 168(9): 4382 - 4390. [Abstract] [Full Text] [PDF]
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G. J. D. van Mierlo, A. Th. den Boer, J. P. Medema, E. I. H. van der Voort, M. F. Fransen, R. Offringa, C. J. M. Melief, and R. E. M. Toes CD40 stimulation leads to effective therapy of CD40- tumors through induction of strong systemic cytotoxic T lymphocyte immunity PNAS, April 16, 2002; 99(8): 5561 - 5566. [Abstract] [Full Text] [PDF]
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L. Diehl, G. J. D. van Mierlo, A. T. den Boer, E. van der Voort, M. Fransen, L. van Bostelen, P. Krimpenfort, C. J. M. Melief, R. Mittler, R. E. M. Toes, et al. In Vivo Triggering Through 4-1BB Enables Th-Independent Priming of CTL in the Presence of an Intact CD28 Costimulatory Pathway J. Immunol., April 15, 2002; 168(8): 3755 - 3762. [Abstract] [Full Text] [PDF]
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E. M. Bertram, P. Lau, and T. H. Watts Temporal Segregation of 4-1BB Versus CD28-Mediated Costimulation: 4-1BB Ligand Influences T Cell Numbers Late in the Primary Response and Regulates the Size of the T Cell Memory Response Following Influenza Infection J. Immunol., April 15, 2002; 168(8): 3777 - 3785. [Abstract] [Full Text] [PDF]
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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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K. Nozawa, J. Ohata, J. Sakurai, H. Hashimoto, H. Miyajima, H. Yagita, K. Okumura, and M. Azuma Preferential Blockade of CD8+ T Cell Responses by Administration of Anti-CD137 Ligand Monoclonal Antibody Results in Differential Effect on Development of Murine Acute and Chronic Graft-Versus-Host Diseases J. Immunol., November 1, 2001; 167(9): 4981 - 4986. [Abstract] [Full Text] [PDF]
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G. Zhu, D. B. Flies, K. Tamada, Y. Sun, M. Rodriguez, Y.-X. Fu, and L. Chen Progressive Depletion of Peripheral B Lymphocytes in 4-1BB (CD137) Ligand/I-E{alpha}-Transgenic Mice J. Immunol., September 1, 2001; 167(5): 2671 - 2676. [Abstract] [Full Text] [PDF]
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J. L. Cannons, P. Lau, B. Ghumman, M. A. DeBenedette, H. Yagita, K. Okumura, and T. H. Watts 4-1BB Ligand Induces Cell Division, Sustains Survival, and Enhances Effector Function of CD4 and CD8 T Cells with Similar Efficacy J. Immunol., August 1, 2001; 167(3): 1313 - 1324. [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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J. L. Cannons, Y. Choi, and T. H. Watts Role of TNF Receptor-Associated Factor 2 and p38 Mitogen-Activated Protein Kinase Activation During 4-1BB-Dependent Immune Response J. Immunol., December 1, 2000; 165(11): 6193 - 6204. [Abstract] [Full Text] [PDF]
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I. Gramaglia, A. Jember, S. D. Pippig, A. D. Weinberg, N. Killeen, and M. Croft The OX40 Costimulatory Receptor Determines the Development of CD4 Memory by Regulating Primary Clonal Expansion J. Immunol., September 15, 2000; 165(6): 3043 - 3050. [Abstract] [Full Text] [PDF]
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R. S. Kornbluth The emerging role of CD40 ligand in HIV infection J. Leukoc. Biol., September 1, 2000; 68(3): 373 - 382. [Abstract] [Full Text] [PDF]
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H. R. Salih, S. G. Kosowski, V. F. Haluska, G. C. Starling, D. T. Loo, F. Lee, A. A. Aruffo, P. A. Trail, and P. A. Kiener Constitutive Expression of Functional 4-1BB (CD137) Ligand on Carcinoma Cells J. Immunol., September 1, 2000; 165(5): 2903 - 2910. [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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I. Suzuki and P. J. Fink The dual functions of Fas ligand in the regulation of peripheral CD8+ and CD4+ T cells PNAS, February 15, 2000; 97(4): 1707 - 1712. [Abstract] [Full Text] [PDF]
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S. D. Pippig, C. Pena-Rossi, J. Long, W. R. Godfrey, D. J. Fowell, S. L. Reiner, M. L. Birkeland, R. M. Locksley, A. N. Barclay, and N. Killeen Robust B Cell Immunity but Impaired T Cell Proliferation in the Absence of CD134 (OX40) J. Immunol., December 15, 1999; 163(12): 6520 - 6529. [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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G. J. D. van Mierlo, A. Th. den Boer, J. P. Medema, E. I. H. van der Voort, M. F. Fransen, R. Offringa, C. J. M. Melief, and R. E. M. Toes CD40 stimulation leads to effective therapy of CD40- tumors through induction of strong systemic cytotoxic T lymphocyte immunity PNAS, April 16, 2002; 99(8): 5561 - 5566. [Abstract] [Full Text] [PDF]
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N. Arbour, D. Naniche, D. Homann, R. J. Davis, R. A. Flavell, and M. B.A. Oldstone c-Jun NH2-Terminal Kinase (JNK)1 and JNK2 Signaling Pathways Have Divergent Roles in CD8+ T Cell-mediated Antiviral Immunity J. Exp. Med., March 25, 2002; 195(7): 801 - 810. [Abstract] [Full Text] [PDF]
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