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
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Antov, A.
Right arrow Articles by Van Parijs, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Antov, A.
Right arrow Articles by Van Parijs, L.
The Journal of Immunology, 2003, 171: 3435-3441.
Copyright © 2003 by The American Association of Immunologists

Essential Role for STAT5 Signaling in CD25+CD4+ Regulatory T Cell Homeostasis and the Maintenance of Self-Tolerance1

Andrey Antov*, Lili Yang{dagger}, Monika Vig*, David Baltimore{dagger} and Luk Van Parijs2,*

* Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139; and {dagger} Department of Biology, California Institute of Technology, Pasadena, CA 91125

A population of CD25+CD4+ regulatory T cells (T regs) functions to maintain immunological self tolerance by inhibiting autoreactive T cell responses. CD25+CD4+ T regs are present in low, but steady, numbers in the peripheral lymphoid tissues of healthy mice. Recent studies have shown that IL-2 is an essential growth factor for these cells. How this cytokine functions to regulate CD25+CD4+ T reg homeostasis and prevent autoimmune disease remains unknown. In conventional CD4+ T cells, IL-2 triggers signaling pathways that promote proliferation and survival by activating the STAT5 transcription factor and by increasing the expression of the antiapoptotic protein, Bcl-2. We show here that bcl-2 deficiency does not affect CD25+CD4+ T reg homeostasis, and that ectopic expression of this molecule fails to rescue CD25+CD4+ T reg numbers or to prevent the development of autoimmunity in IL-2-deficient mice. Furthermore, transient activation of STAT5 is sufficient to increase CD25+CD4+ T reg numbers in IL-2-deficient mice. Our study uncovers an essential role for STAT5 in maintaining CD25+CD4+ T reg homeostasis and self-tolerance.




This article has been cited by other articles:


Home page
 BloodHome page
H. Kared, B. Leforban, R. Montandon, A. Renand, E. Layseca Espinosa, L. Chatenoud, Y. Rosenstein, E. Schneider, M. Dy, and F. Zavala
Role of GM-CSF in tolerance induction by mobilized hematopoietic progenitors
Blood, September 15, 2008; 112(6): 2575 - 2578.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. L. Bayer, J. Y. Lee, A. de la Barrera, C. D. Surh, and T. R. Malek
A Function for IL-7R for CD4+CD25+Foxp3+ T Regulatory Cells
J. Immunol., July 1, 2008; 181(1): 225 - 234.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
R. Zeiser, D. B. Leveson-Gower, E. A. Zambricki, N. Kambham, A. Beilhack, J. Loh, J.-Z. Hou, and R. S. Negrin
Differential impact of mammalian target of rapamycin inhibition on CD4+CD25+Foxp3+ regulatory T cells compared with conventional CD4+ T cells
Blood, January 1, 2008; 111(1): 453 - 462.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
J. Yates, F. Rovis, P. Mitchell, B. Afzali, J.-S Tsang, M. Garin, R. Lechler, G. Lombardi, and O. Garden
The maintenance of human CD4+CD25+ regulatory T cell function: IL-2, IL-4, IL-7 and IL-15 preserve optimal suppressive potency in vitro
Int. Immunol., June 1, 2007; 19(6): 785 - 799.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
Z. Yao, Y. Kanno, M. Kerenyi, G. Stephens, L. Durant, W. T. Watford, A. Laurence, G. W. Robinson, E. M. Shevach, R. Moriggl, et al.
Nonredundant roles for Stat5a/b in directly regulating Foxp3
Blood, May 15, 2007; 109(10): 4368 - 4375.
[Abstract] [Full Text] [PDF]

Home page
 PediatricsHome page
A. Bernasconi, R. Marino, A. Ribas, J. Rossi, M. Ciaccio, M. Oleastro, A. Ornani, R. Paz, M. A. Rivarola, M. Zelazko, et al.
Characterization of Immunodeficiency in a Patient With Growth Hormone Insensitivity Secondary to a Novel STAT5b Gene Mutation
Pediatrics, November 1, 2006; 118(5): e1584 - e1592.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
A. Toda and C. A. Piccirillo
Development and function of naturally occurring CD4+CD25+ regulatory T cells
J. Leukoc. Biol., September 1, 2006; 80(3): 458 - 470.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. C. Cohen, K. C. Nadeau, W. Tu, V. Hwa, K. Dionis, L. Bezrodnik, A. Teper, M. Gaillard, J. Heinrich, A. M. Krensky, et al.
Cutting Edge: Decreased Accumulation and Regulatory Function of CD4+CD25high T Cells in Human STAT5b Deficiency.
J. Immunol., September 1, 2006; 177(5): 2770 - 2774.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
E. Zorn, E. A. Nelson, M. Mohseni, F. Porcheray, H. Kim, D. Litsa, R. Bellucci, E. Raderschall, C. Canning, R. J. Soiffer, et al.
IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT-dependent mechanism and induces the expansion of these cells in vivo
Blood, September 1, 2006; 108(5): 1571 - 1579.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
D. K. Taylor, P. T. Walsh, D. F. LaRosa, J. Zhang, M. A. Burchill, M. A. Farrar, and L. A. Turka
Constitutive Activation of STAT5 Supersedes the Requirement for Cytokine and TCR Engagement of CD4+ T Cells in Steady-State Homeostasis
J. Immunol., August 15, 2006; 177(4): 2216 - 2223.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
P. A. Antony, C. M. Paulos, M. Ahmadzadeh, A. Akpinarli, D. C. Palmer, N. Sato, A. Kaiser, C. Heinrichs, C. A. Klebanoff, Y. Tagaya, et al.
Interleukin-2-Dependent Mechanisms of Tolerance and Immunity In Vivo
J. Immunol., May 1, 2006; 176(9): 5255 - 5266.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Z. Yao, Y. Cui, W. T. Watford, J. H. Bream, K. Yamaoka, B. D. Hissong, D. Li, S. K. Durum, Q. Jiang, A. Bhandoola, et al.
Stat5a/b are essential for normal lymphoid development and differentiation
PNAS, January 24, 2006; 103(4): 1000 - 1005.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Med.Home page
S. Koonpaew, S. Shen, L. Flowers, and W. Zhang
LAT-mediated signaling in CD4+CD25+ regulatory T cell development
J. Exp. Med., January 23, 2006; 203(1): 119 - 129.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y. Zhang, R. A. Kirken, L. Furian, S. Janczewska, X. Qu, W. W. Hancock, M. Wang, N. Tejpal, R. Kerman, B. D. Kahan, et al.
Allograft Rejection Requires STAT5a/b-Regulated Antiapoptotic Activity in T Cells but Not B Cells
J. Immunol., January 1, 2006; 176(1): 128 - 137.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Med.Home page
R. Setoguchi, S. Hori, T. Takahashi, and S. Sakaguchi
Homeostatic maintenance of natural Foxp3+ CD25+ CD4+ regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization
J. Exp. Med., March 7, 2005; 201(5): 723 - 735.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Med.Home page
A. L. Bayer, A. Yu, D. Adeegbe, and T. R. Malek
Essential role for interleukin-2 for CD4+CD25+ T regulatory cell development during the neonatal period
J. Exp. Med., March 7, 2005; 201(5): 769 - 777.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
P. A. Antony, C. A. Piccirillo, A. Akpinarli, S. E. Finkelstein, P. J. Speiss, D. R. Surman, D. C. Palmer, C.-C. Chan, C. A. Klebanoff, W. W. Overwijk, et al.
CD8+ T Cell Immunity Against a Tumor/Self-Antigen Is Augmented by CD4+ T Helper Cells and Hindered by Naturally Occurring T Regulatory Cells
J. Immunol., March 1, 2005; 174(5): 2591 - 2601.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
P. O. Anderson, A. Sundstedt, Z. Yazici, S. Minaee, R. Woolf, K. Nicolson, N. Whitley, L. Li, S. Li, D. C. Wraith, et al.
IL-2 Overcomes the Unresponsiveness but Fails to Reverse the Regulatory Function of Antigen-Induced T Regulatory Cells
J. Immunol., January 1, 2005; 174(1): 310 - 319.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. A. Curotto de Lafaille, A. C. Lino, N. Kutchukhidze, and J. J. Lafaille
CD25- T Cells Generate CD25+Foxp3+ Regulatory T Cells by Peripheral Expansion
J. Immunol., December 15, 2004; 173(12): 7259 - 7268.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. M. Thornton, E. E. Donovan, C. A. Piccirillo, and E. M. Shevach
Cutting Edge: IL-2 Is Critically Required for the In Vitro Activation of CD4+CD25+ T Cell Suppressor Function
J. Immunol., June 1, 2004; 172(11): 6519 - 6523.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
B. H. Nelson
IL-2, Regulatory T Cells, and Tolerance
J. Immunol., April 1, 2004; 172(7): 3983 - 3988.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. Schmidt-Supprian, J. Tian, E. P. Grant, M. Pasparakis, R. Maehr, H. Ovaa, H. L. Ploegh, A. J. Coyle, and K. Rajewsky
Differential dependence of CD4+CD25+ regulatory and natural killer-like T cells on signals leading to NF-{kappa}B activation
PNAS, March 30, 2004; 101(13): 4566 - 4571.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2003 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2003 by The American Association of Immunologists, Inc. All rights reserved.