The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

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
Right arrow Citation Map
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 Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhou, G.
Right arrow Articles by Levitsky, H. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhou, G.
Right arrow Articles by Levitsky, H. I.
The Journal of Immunology, 2007, 178: 2155-2162.
Copyright © 2007 by The American Association of Immunologists, Inc.

Natural Regulatory T Cells and De Novo-Induced Regulatory T Cells Contribute Independently to Tumor-Specific Tolerance1

Gang Zhou and Hyam I. Levitsky2

Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, MD 21231

Thymus-derived, naturally occurring CD4+CD25+Foxp3+ regulatory T cells (nTregs) and Tregs induced in the periphery (iTregs) have both been implicated in regulating immune responses. However, the relationship between these populations in the same host, and their relative contribution to the overall Treg pool, has not been examined. Using a tumor-induced T cell tolerance model, we find that expansion of nTregs and de novo generation of iTregs both contribute to tumor-specific T cell tolerance. In this system in which the number of tumor-specific nTregs can be controlled, the efficiency of nTreg expansion significantly exceeds that of the induction of Tregs from uncommitted progenitors in the tumor-bearing host. However, pre-existing nTregs are neither required for the induction of Tregs nor measurably impact on the extent of their accumulation. Instead, induction of Ag-specific regulatory cells from naive cells is intrinsically influenced by the tumor microenvironment and the presence of tumor Ag.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by Grants CA96888-01 and CA15396-23 from National Institutes of Health.

2 Address correspondence and reprint requests to Dr. Hyam I. Levitsky, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 1650 Orleans Street, Suite 4M51, Baltimore, MD 21231. E-mail address: hy{at}jhmi.edu

3 Abbreviations used in this paper: Treg, regulatory T cell; nTreg, naturally occurring CD4+CD25+Foxp3+ Treg; iTreg, induced Treg; GITR, glucocorticoid-induced TNFR; HA, hemagglutinin; Tg, transgenic; vacHA, vaccinia virus encoding HA; DC, dendritic cell.




This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
M. G. LaCelle, S. M. Jensen, and B. A. Fox
Partial CD4 Depletion Reduces Regulatory T Cells Induced by Multiple Vaccinations and Restores Therapeutic Efficacy
Clin. Cancer Res., November 15, 2009; 15(22): 6881 - 6890.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Jandus, G. Bioley, D. Dojcinovic, L. Derre, L. Baitsch, S. Wieckowski, N. Rufer, W. W. Kwok, J.-M. Tiercy, I. F. Luescher, et al.
Tumor Antigen-Specific FOXP3+ CD4 T Cells Identified in Human Metastatic Melanoma: Peptide Vaccination Results in Selective Expansion of Th1-like Counterparts
Cancer Res., October 15, 2009; 69(20): 8085 - 8093.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
I. Horkheimer, M. Quigley, J. Zhu, X. Huang, N. J. Chao, and Y. Yang
Induction of type I IFN is required for overcoming tumor-specific T-cell tolerance after stem cell transplantation
Blood, May 21, 2009; 113(21): 5330 - 5339.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
D. Getnet, C. H. Maris, E. L. Hipkiss, J. F. Grosso, T. J. Harris, H.-R. Yen, T. C. Bruno, S. Wada, A. Adler, R. W. Georgantas, et al.
Tumor Recognition and Self-Recognition Induce Distinct Transcriptional Profiles in Antigen-Specific CD4 T Cells
J. Immunol., April 15, 2009; 182(8): 4675 - 4685.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. Ahmadzadeh, A. Felipe-Silva, B. Heemskerk, D. J. Powell Jr, J. R. Wunderlich, M. J. Merino, and S. A. Rosenberg
FOXP3 expression accurately defines the population of intratumoral regulatory T cells that selectively accumulate in metastatic melanoma lesions
Blood, December 15, 2008; 112(13): 4953 - 4960.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
M. Kovar, J. Tomala, H. Chmelova, L. Kovar, T. Mrkvan, R. Joskova, Z. Zakostelska, T. Etrych, J. Strohalm, K. Ulbrich, et al.
Overcoming Immunoescape Mechanisms of BCL1 Leukemia and Induction of CD8+ T-Cell-Mediated BCL1-Specific Resistance in Mice Cured by Targeted Polymer-Bound Doxorubicin
Cancer Res., December 1, 2008; 68(23): 9875 - 9883.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. L. Tang, J. R. Teijaro, M. N. Njau, S. S. Chandran, A. Azimzadeh, S. G. Nadler, D. M. Rothstein, and D. L. Farber
CTLA4 Expression Is an Indicator and Regulator of Steady-State CD4+FoxP3+ T Cell Homeostasis
J. Immunol., August 1, 2008; 181(3): 1806 - 1813.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
P. Serafini, S. Mgebroff, K. Noonan, and I. Borrello
Myeloid-Derived Suppressor Cells Promote Cross-Tolerance in B-Cell Lymphoma by Expanding Regulatory T Cells
Cancer Res., July 1, 2008; 68(13): 5439 - 5449.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
C. Bergmann, L. Strauss, Y. Wang, M. J. Szczepanski, S. Lang, J. T. Johnson, and T. L. Whiteside
T Regulatory Type 1 Cells in Squamous Cell Carcinoma of the Head and Neck: Mechanisms of Suppression and Expansion in Advanced Disease
Clin. Cancer Res., June 15, 2008; 14(12): 3706 - 3715.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
S. Piconese, B. Valzasina, and M. P. Colombo
OX40 triggering blocks suppression by regulatory T cells and facilitates tumor rejection
J. Exp. Med., April 14, 2008; 205(4): 825 - 839.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
P. Mirmonsef, G. Tan, G. Zhou, T. Morino, K. Noonan, I. Borrello, and H. I. Levitsky
Escape from suppression: tumor-specific effector cells outcompete regulatory T cells following stem-cell transplantation
Blood, February 15, 2008; 111(4): 2112 - 2121.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
G. S. Deepe Jr. and R. S. Gibbons
TNF-{alpha} Antagonism Generates a Population of Antigen-Specific CD4+CD25+ T Cells That Inhibit Protective Immunity in Murine Histoplasmosis
J. Immunol., January 15, 2008; 180(2): 1088 - 1097.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
L.-F. Lu, M. A. Gavin, J. P. Rasmussen, and A. Y. Rudensky
G Protein-Coupled Receptor 83 Is Dispensable for the Development and Function of Regulatory T Cells
Mol. Cell. Biol., December 1, 2007; 27(23): 8065 - 8072.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
Z.-Z. Yang, A. J. Novak, S. C. Ziesmer, T. E. Witzig, and S. M. Ansell
CD70+ non-Hodgkin lymphoma B cells induce Foxp3 expression and regulatory function in intratumoral CD4+CD25 T cells
Blood, October 1, 2007; 110(7): 2537 - 2544.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2007 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2007 by The American Association of Immunologists, Inc. All rights reserved.