Cancer Research CTRC-AACR San Antonio Breast Cancer Symposium
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Voo, K. S.
Right arrow Articles by Wang, R.-F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Voo, K. S.
Right arrow Articles by Wang, R.-F.
[Cancer Research 65, 1577-1586, February 15, 2005]
© 2005 American Association for Cancer Research

Immunology

Functional Characterization of EBV-Encoded Nuclear Antigen 1–Specific CD4+ Helper and Regulatory T Cells Elicited by In vitro Peptide Stimulation

Kui Shin Voo1,2, Guangyong Peng1, Zhong Guo1, Tihui Fu1, Yanchun Li1, Lori Frappier3 and Rong-Fu Wang1,2

1 The Center for Cell and Gene Therapy and 2 Department of Immunology, Baylor College of Medicine, Houston, Texas; and 3 Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Ontario, Canada

Requests for reprints: Rong-Fu Wang, The Center for Cell and Gene Therapy, Baylor College of Medicine, ALKEK Building, N1120, One Baylor Plaza, Houston, TX 77030. Phone: 713-798-1244; Fax: 713-798-1263; E-mail: rongfuw{at}bcm.tmc.edu.

CD4+ helper and regulatory T (Treg) cells play important but opposing roles in regulating host immune responses against cancer and other diseases. However, very little is known about the antigen specificity of CD4+ Treg cells. Here we describe the generation of a panel of EBV-encoded nuclear antigen 1 (EBNA1)–specific CD4+ T-cell lines and clones that recognize naturally processed EBNA1-P607-619 and -P561-573 peptides in the context of HLA-DQ2 and HLA-DR11, -DR12, and -DR13 molecules, respectively. Phenotypic and functional analyses of these CD4+ T cells revealed that they represent EBNA1-specific CD4+ T helper as well as Treg cells. CD4+ Treg cells do not secrete interleukin (IL)-10 and transforming growth factor ß cytokines but express CD25, the glucocorticoid-induced tumor necrosis factor receptor–related protein (GITR), and Forkhead Box P3 (Foxp3), and are capable of suppressing the proliferative responses of naïve CD4+ and CD8+ T cells to stimulation with mitogenic anti-CD3 antibody. The suppressive activity of these CD4+ Treg cells is mediated via cell-cell contact or in part by a cytokine-dependent manner. Importantly, these Treg cells suppress IL-2 secretion by CD4+ effector T cells specific for either EBNA1 or a melanoma antigen, suggesting that these CD4+ Treg cells induce immune suppression. These observations suggest that the success of peptide-based vaccines against EBV-associated cancer and other diseases may likely depend upon our ability to identify antigens/peptides that preferentially activate helper T cells and/or to design strategies to regulate the balance between CD4+ helper and Treg cells.

Key Words: Tumor Immunity • Vaccination • Regulatory T cells • T Lymphocytes • EBV Antigens




This article has been cited by other articles:


Home page
 Cancer Res.Home page
H. Kobayashi, T. Nagato, M. Takahara, K. Sato, S. Kimura, N. Aoki, M. Azumi, M. Tateno, Y. Harabuchi, and E. Celis
Induction of EBV-Latent Membrane Protein 1-Specific MHC Class II-Restricted T-Cell Responses against Natural Killer Lymphoma Cells
Cancer Res., February 1, 2008; 68(3): 901 - 908.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. A. Fernandez, F. K. Puttur, Y. M. Wang, W. Howden, S. I. Alexander, and C. A. Jones
T Regulatory Cells Contribute to the Attenuated Primary CD8+ and CD4+ T Cell Responses to Herpes Simplex Virus Type 2 in Neonatal Mice
J. Immunol., February 1, 2008; 180(3): 1556 - 1564.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
S. Li, E. J. Gowans, C. Chougnet, M. Plebanski, and U. Dittmer
Natural Regulatory T Cells and Persistent Viral Infection
J. Virol., January 1, 2008; 82(1): 21 - 30.
[Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
P. Hubert, N. Jacobs, J.-H. Caberg, J. Boniver, and P. Delvenne
The cross-talk between dendritic and regulatory T cells: good or evil?
J. Leukoc. Biol., October 1, 2007; 82(4): 781 - 794.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
A. Diepstra, G. W. van Imhoff, H. E. Karim-Kos, A. van den Berg, G. J. te Meerman, M. Niens, I. M. Nolte, E. Bastiaannet, M. Schaapveld, E. Vellenga, et al.
HLA Class II Expression by Hodgkin Reed-Sternberg Cells Is an Independent Prognostic Factor in Classical Hodgkin's Lymphoma
J. Clin. Oncol., July 20, 2007; 25(21): 3101 - 3108.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. H. van der Burg, S. J. Piersma, A. de Jong, J. M. van der Hulst, K. M. C. Kwappenberg, M. van den Hende, M. J. P. Welters, J. J. Van Rood, G. J. Fleuren, C. J. M. Melief, et al.
Association of cervical cancer with the presence of CD4+ regulatory T cells specific for human papillomavirus antigens
PNAS, July 17, 2007; 104(29): 12087 - 12092.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. Nagato, H. Kobayashi, M. Yanai, K. Sato, N. Aoki, K. Oikawa, S. Kimura, Y. Abe, E. Celis, Y. Harabuchi, et al.
Functional Analysis of Birch Pollen Allergen Bet v 1-Specific Regulatory T Cells
J. Immunol., January 15, 2007; 178(2): 1189 - 1198.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. M. Miller, K. Lundberg, V. Ozenci, A. H. Banham, M. Hellstrom, L. Egevad, and P. Pisa
CD4+CD25high T Cells Are Enriched in the Tumor and Peripheral Blood of Prostate Cancer Patients
J. Immunol., November 15, 2006; 177(10): 7398 - 7405.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. K. Gandhi, E. Lambley, J. Duraiswamy, U. Dua, C. Smith, S. Elliott, D. Gill, P. Marlton, J. Seymour, and R. Khanna
Expression of LAG-3 by tumor-infiltrating lymphocytes is coincident with the suppression of latent membrane antigen-specific CD8+ T-cell function in Hodgkin lymphoma patients
Blood, October 1, 2006; 108(7): 2280 - 2289.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
J. D. Lunemann, N. Edwards, P. A. Muraro, S. Hayashi, J. I. Cohen, C. Munz, and R. Martin
Increased frequency and broadened specificity of latent EBV nuclear antigen-1-specific T cells in multiple sclerosis
Brain, June 1, 2006; 129(6): 1493 - 1506.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R.-F. Wang
Regulatory T cells and toll-like receptors in cancer therapy.
Cancer Res., May 15, 2006; 66(10): 4987 - 4990.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
Y.-Q. Chen, H.-Z. Shi, X.-J. Qin, W.-N. Mo, X.-D. Liang, Z.-X. Huang, H.-B. Yang, and C. Wu
CD4+CD25+ Regulatory T Lymphocytes in Malignant Pleural Effusion
Am. J. Respir. Crit. Care Med., December 1, 2005; 172(11): 1434 - 1439.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2005 by the American Association for Cancer Research.