| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
The Carlos and Marguerite Mason Transplantation Biology Research Center and Department of Surgery, and
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322; and
Epimmune, San Diego, CA 92121
Peptide vaccination induces T cell activation and cytotoxic T cell
development. In an effort to understand what factors can improve immune
responses to peptide vaccination, the role of 4-1BB (CD137)
costimulation was examined, since 4-1BB has been shown to promote T
cell responses in other systems. 4-1BBL-deficient (-/-) and wild-type
(+/+) mice were immunized with a lipidated lymphocytic choriomeningitis
virus (LCMV) peptide NP396–404. Analysis of
peptide-specific responses early after immunization by CTL assay,
intracellular IFN-
staining, and IFN- enzyme-linked immunospot
assay (ELISPOT) indicated that CD8 T cell responses were reduced 3- to
10-fold in the absence of 4-1BB costimulation. Moreover, when agonistic
anti-4-1BB Ab was given, CD8 T cell responses in
4-1BBL-/- mice were augmented to levels similar to those
in 4-1BBL+/+ mice. Two months after immunization,
4-1BBL+/+ mice still had epitope-specific cells and were
protected against viral challenge, demonstrating that peptide
vaccination can induce long-term protection. In fact, 70% of CD8 T
cells were specific for the immunizing peptide after viral challenge,
demonstrating that strong, epitope-specific CD8 T cell responses are
generated after peptide vaccination. In contrast, peptide-immunized
4-1BBL-/- mice had fewer epitope-specific cells and were
impaired in their ability to resolve the infection. These results show
that immunization with a single LCMV peptide provides long term
protection against LCMV infection and point to costimulatory molecules
such as 4-1BB as important components for generating protective
immunity after vaccination.
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
|
|
|
|
K. G. Elpek, E. S. Yolcu, D. D. H. Franke, C. Lacelle, R.-H. Schabowsky, and H. Shirwan Ex Vivo Expansion of CD4+CD25+FoxP3+ T Regulatory Cells Based on Synergy between IL-2 and 4-1BB Signaling J. Immunol., December 1, 2007; 179(11): 7295 - 7304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Fuse, S. Bellfy, H. Yagita, and E. J. Usherwood CD8+ T Cell Dysfunction and Increase in Murine Gammaherpesvirus Latent Viral Burden in the Absence of 4-1BB Ligand J. Immunol., April 15, 2007; 178(8): 5227 - 5236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Niu, S. Strahotin, B. Hewes, B. Zhang, Y. Zhang, D. Archer, T. Spencer, D. Dillehay, B. Kwon, L. Chen, et al. Cytokine-Mediated Disruption of Lymphocyte Trafficking, Hemopoiesis, and Induction of Lymphopenia, Anemia, and Thrombocytopenia in Anti-CD137-Treated Mice J. Immunol., April 1, 2007; 178(7): 4194 - 4213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J Sedgmen, W. Dawicki, J. L Gommerman, K. Pfeffer, and T. H Watts LIGHT is dispensable for CD4+ and CD8+ T cell and antibody responses to influenza A virus in mice Int. Immunol., May 1, 2006; 18(5): 797 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Wuthrich, P. L. Fisette, H. I. Filutowicz, and B. S. Klein Differential Requirements of T Cell Subsets for CD40 Costimulation in Immunity to Blastomyces dermatitidis J. Immunol., May 1, 2006; 176(9): 5538 - 5547. [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]
|
|
|
|
|
|
K. E. Foulds and H. Shen Clonal Competition Inhibits the Proliferation and Differentiation of Adoptively Transferred TCR Transgenic CD4 T Cells in Response to Infection. J. Immunol., March 1, 2006; 176(5): 3037 - 3043. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. Kemball, E. D. H. Lee, E. Szomolanyi-Tsuda, T. C. Pearson, C. P. Larsen, and A. E. Lukacher Costimulation Requirements for Antiviral CD8+ T Cells Differ for Acute and Persistent Phases of Polyoma Virus Infection J. Immunol., February 1, 2006; 176(3): 1814 - 1824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Serghides, J. Bukczynski, T. Wen, C. Wang, J.-P. Routy, M.-R. Boulassel, R.-P. Sekaly, M. Ostrowski, N. F. Bernard, and T. H. Watts Evaluation of OX40 Ligand as a Costimulator of Human Antiviral Memory CD8 T Cell Responses: Comparison with B7.1 and 4-1BBL J. Immunol., November 15, 2005; 175(10): 6368 - 6377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Bukczynski, T. Wen, C. Wang, N. Christie, J.-P. Routy, M.-R. Boulassel, C. M. Kovacs, K. S. MacDonald, M. Ostrowski, R.-P. Sekaly, et al. Enhancement of HIV-Specific CD8 T Cell Responses by Dual Costimulation with CD80 and CD137L J. Immunol., November 15, 2005; 175(10): 6378 - 6389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Fukushima, T. Yamaguchi, W. Ishida, K. Fukata, R. S. Mittler, H. Yagita, and H. Ueno Engagement of 4-1BB Inhibits the Development of Experimental Allergic Conjunctivitis in Mice J. Immunol., October 15, 2005; 175(8): 4897 - 4903. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Terrasson, S. Allart, H. Martin, J. Lule, H. Haddada, D. Caput, and C. Davrinche p73-Dependent Apoptosis through Death Receptor: Impairment by Human Cytomegalovirus Infection Cancer Res., April 1, 2005; 65(7): 2787 - 2794. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-J. Kim, T. M. Stringfield, Y. Chen, and H. E. Broxmeyer Modulation of cord blood CD8+ T-cell effector differentiation by TGF-{beta}1 and 4-1BB costimulation Blood, January 1, 2005; 105(1): 274 - 281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Dawicki, E. M. Bertram, A. H. Sharpe, and T. H. Watts 4-1BB and OX40 Act Independently to Facilitate Robust CD8 and CD4 Recall Responses J. Immunol., November 15, 2004; 173(10): 5944 - 5951. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Wherry and R. Ahmed Memory CD8 T-Cell Differentiation during Viral Infection J. Virol., June 1, 2004; 78(11): 5535 - 5545. [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]
|
|
|
|
 |
|
 J. Bukczynski, T. Wen, K. Ellefsen, J. Gauldie, and T. H. Watts Costimulatory ligand 4-1BBL (CD137L) as an efficient adjuvant for human antiviral cytotoxic T cell responses PNAS, February 3, 2004; 101(5): 1291 - 1296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Bertram, W. Dawicki, B. Sedgmen, J. L. Bramson, D. H. Lynch, and T. H. Watts A Switch in Costimulation from CD28 to 4-1BB during Primary versus Secondary CD8 T Cell Response to Influenza In Vivo J. Immunol., January 15, 2004; 172(2): 981 - 988. [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]
|
|
|
|
 |
|
 F. G. Lakkis and M. H. Sayegh Memory T Cells: A Hurdle to Immunologic Tolerance J. Am. Soc. Nephrol., September 1, 2003; 14(9): 2402 - 2410. [Full Text] [PDF]
|
|
|
|
 |
|
 J. FOELL, M. McCAUSLAND, J. BURCH, N. CORRIAZZI, X.-J. YAN, C. SUWYN, S. P. O'NEIL, M. K. HOFFMANN, and R. S. MITTLER CD137-Mediated T Cell Co-Stimulation Terminates Existing Autoimmune Disease in SLE-Prone NZB/NZW F1 Mice Ann. N.Y. Acad. Sci., April 1, 2003; 987(1): 230 - 235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
R. A. Wilcox, K. Tamada, S. E. Strome, and L. Chen Signaling Through NK Cell-Associated CD137 Promotes Both Helper Function for CD8+ Cytolytic T Cells and Responsiveness to IL-2 But Not Cytolytic Activity J. Immunol., October 15, 2002; 169(8): 4230 - 4236. [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]
|
|
|
|
|
|
J. L. Cannons, E. M. Bertram, and T. H. Watts Cutting Edge: Profound Defect in T Cell Responses in TNF Receptor-Associated Factor 2 Dominant Negative Mice J. Immunol., September 15, 2002; 169(6): 2828 - 2831. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wirths, J. Reichert, F. Grunebach, and P. Brossart Activated CD8+ T Lymphocytes Induce Differentiation of Monocytes to Dendritic Cells and Restore the Stimulatory Capacity of Interleukin 10-treated Antigen-presenting Cells Cancer Res., September 1, 2002; 62(17): 5065 - 5068. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Wilcox, D. B. Flies, H. Wang, K. Tamada, A. J. Johnson, L. R. Pease, M. Rodriguez, Y. Guo, and L. Chen Impaired Infiltration of Tumor-specific Cytolytic T Cells in the Absence of Interferon-{gamma} despite Their Normal Maturation in Lymphoid Organs during CD137 Monoclonal Antibody Therapy Cancer Res., August 1, 2002; 62(15): 4413 - 4418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. F. May Jr., L. Chen, P. Zheng, and Y. Liu Anti-4-1BB Monoclonal Antibody Enhances Rejection of Large Tumor Burden by Promoting Survival but not Clonal Expansion of Tumor-specific CD8+ T Cells Cancer Res., June 1, 2002; 62(12): 3459 - 3465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. S. Kwon, J. C. Hurtado, Z. H. Lee, K. B. Kwack, S. K. Seo, B. K. Choi, B. H. Koller, G. Wolisi, H. E. Broxmeyer, and D. S. Vinay Immune Responses in 4-1BB (CD137)-Deficient Mice J. Immunol., June 1, 2002; 168(11): 5483 - 5490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
A. Tawab, J. Fields, E. Chao, and R. J. Kurlander Recombinant lemA without adjuvant induces extensive expansion of H2-M3-restricted CD8 effectors, which can suppress primary listeriosis in mice Int. Immunol., February 1, 2002; 14(2): 225 - 232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Prlic, B. R. Blazar, A. Khoruts, T. Zell, and S. C. Jameson Homeostatic Expansion Occurs Independently of Costimulatory Signals J. Immunol., November 15, 2001; 167(10): 5664 - 5668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
J. M. M. den Haan and M. J. Bevan A novel helper role for CD4 T cells PNAS, November 21, 2000; 97(24): 12950 - 12952. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
