| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Immunohematology and Bloodtransfusion, Leiden University Medical Center, Leiden, The Netherlands;
Division of Molecular Genetics and Center of Biomedical Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands; and
Vaccine Research Center, Emory University, Atlanta, GA 30329
Triggering of 4-1BB, a member of the TNFR family, through in vivo administration of agonistic anti-4-1BB Ab delivers a powerful costimulatory signal to CTL. We found this signal to effectively replace the need for CD4+ T cell help in the cross-priming of tumor-specific CTL immunity. Furthermore, 4-1BB Ab can convert an otherwise tolerogenic peptide vaccine into a formulation capable of efficient CTL priming. Initial activation of naive CTL can occur in the absence of 4-1BB costimulation, but this signal permits increased survival of Ag-stimulated CTL. Because naive CTL do not express 4-1BB at their surface, susceptibility to 4-1BB triggering depends on prior up-regulation of this receptor. We show that this requires both stimulation of the TCR and CD28-dependent costimulation. Accordingly, blockade of the CD28-costimulatory pathway abrogates the capacity of agonistic anti-4-1BB Ab to trigger Th-independent CTL immunity. In conclusion, our data reveal that the 4-1BB-mediated survival signal is positioned downstream of Ag-specific TCR triggering and CD28-dependent costimulation of naive CTL. The powerful effects of 4-1BB triggering on the induction, amplification, and persistence of CTL responses provide a novel strategy for increasing the potency of vaccines against cancers.
This article has been cited by other articles:
|
|
 |
|
  J. Kim, K. Park, H. J. Kim, J. Kim, H.-A Kim, D. Jung, H. J. Kim, H.-J. Choi, S.-Y. Choi, K. W. Seo, et al. Breaking of CD8+ T Cell Tolerance through In Vivo Ligation of CD40 Results in Inhibition of Chronic Graft-versus-Host Disease and Complete Donor Cell Engraftment J. Immunol., November 15, 2008; 181(10): 7380 - 7389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Murillo, A. Arina, S. Hervas-Stubbs, A. Gupta, B. McCluskey, J. Dubrot, A. Palazon, A. Azpilikueta, M. C. Ochoa, C. Alfaro, et al. Therapeutic Antitumor Efficacy of Anti-CD137 Agonistic Monoclonal Antibody in Mouse Models of Myeloma Clin. Cancer Res., November 1, 2008; 14(21): 6895 - 6906. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. N. Golovina, T. Mikheeva, M. M. Suhoski, N. A. Aqui, V. C. Tai, X. Shan, R. Liu, R. R. Balcarcel, N. Fisher, B. L. Levine, et al. CD28 Costimulation Is Essential for Human T Regulatory Expansion and Function J. Immunol., August 15, 2008; 181(4): 2855 - 2868. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Robertson, R. J. Messer, A. B. Carmody, R. S. Mittler, C. Burlak, and K. J. Hasenkrug CD137 Costimulation of CD8+ T Cells Confers Resistance to Suppression by Virus-Induced Regulatory T Cells J. Immunol., April 15, 2008; 180(8): 5267 - 5274. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. French, V. Y. Taraban, G. R. Crowther, T. F. Rowley, J. C. Gray, P. W. Johnson, A. L. Tutt, A. Al-Shamkhani, and M. J. Glennie Eradication of lymphoma by CD8 T cells following anti-CD40 monoclonal antibody therapy is critically dependent on CD27 costimulation Blood, June 1, 2007; 109(11): 4810 - 4815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Zhang, R. E. Sadun, R. S. Arias, M. L. Flanagan, S. M. Sachsman, Y.-C. Nien, L. A. Khawli, P. Hu, and A. L. Epstein Targeted and Untargeted CD137L Fusion Proteins for the Immunotherapy of Experimental Solid Tumors Clin. Cancer Res., May 1, 2007; 13(9): 2758 - 2767. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Y. Taraban, T. F. Rowley, D. F. Tough, and A. Al-Shamkhani Requirement for CD70 in CD4+ Th Cell-Dependent and Innate Receptor-Mediated CD8+ T Cell Priming. J. Immunol., September 1, 2006; 177(5): 2969 - 2975. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Stasiolek, A. Bayas, N. Kruse, A. Wieczarkowiecz, K. V. Toyka, R. Gold, and K. Selmaj Impaired maturation and altered regulatory function of plasmacytoid dendritic cells in multiple sclerosis Brain, May 1, 2006; 129(5): 1293 - 1305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Pulle, M. Vidric, and T. H. Watts IL-15-Dependent Induction of 4-1BB Promotes Antigen-Independent CD8 Memory T Cell Survival. J. Immunol., March 1, 2006; 176(5): 2739 - 2748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Y. Taraban, T. F. Rowley, and A. Al-Shamkhani Cutting Edge: A Critical Role for CD70 in CD8 T Cell Priming by CD40-Licensed APCs J. Immunol., December 1, 2004; 173(11): 6542 - 6546. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Bansal-Pakala, B. S. Halteman, M. H.-Y. Cheng, and M. Croft Costimulation of CD8 T Cell Responses by OX40 J. Immunol., April 15, 2004; 172(8): 4821 - 4825. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Wilcox, K. Tamada, D. B. Flies, G. Zhu, A. I. Chapoval, B. R. Blazar, W. M. Kast, and L. Chen Ligation of CD137 receptor prevents and reverses established anergy of CD8+ cytolytic T lymphocytes in vivo Blood, January 1, 2004; 103(1): 177 - 184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
C. Wiethe, K. Dittmar, T. Doan, W. Lindenmaier, and R. Tindle Provision of 4-1BB Ligand Enhances Effector and Memory CTL Responses Generated by Immunization with Dendritic Cells Expressing a Human Tumor-Associated Antigen J. Immunol., March 15, 2003; 170(6): 2912 - 2922. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Douin-Echinard, J.-M. Peron, V. Lauwers-Cances, G. Favre, and B. Couderc Involvement of CD70 and CD80 intracytoplasmic domains in the co-stimulatory signal required to provide an antitumor immune response Int. Immunol., March 1, 2003; 15(3): 359 - 372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 Z.-Q. Wu, A. Q. Khan, Y. Shen, K. M. Wolcott, W. Dawicki, T. H. Watts, R. S. Mittler, and C. M. Snapper 4-1BB (CD137) Differentially Regulates Murine In Vivo Protein- and Polysaccharide-Specific Immunoglobulin Isotype Responses to Streptococcus pneumoniae Infect. Immun., January 1, 2003; 71(1): 196 - 204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
D. Laderach, M. Movassagh, A. Johnson, R. S. Mittler, and A. Galy 4-1BB co-stimulation enhances human CD8+ T cell priming by augmenting the proliferation and survival of effector CD8+ T cells Int. Immunol., October 1, 2002; 14(10): 1155 - 1167. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
