|
|
Blood, 15 November 2004, Vol. 104, No. 10, pp. 3249-3256.
Prepublished online as a Blood First Edition Paper on July 22, 2004; DOI 10.1182/blood-2004-01-0365.
Previous Article | Next Article 
Submitted January 30, 2004
Accepted May 25, 2004
Human immunodeficiency virus-driven expansion of CD4+CD25+ Regulatory T cells Which Suppress HIV-specific CD4 T-cell Responses in HIV-infected Patients
Laurence Weiss*, Vladimira Donkova-Petrini, Laure Caccavelli, Michele Balbo, Cedric Carbonneil, and Yves Levy
INSERM U430 and University Paris V, Paris, France; Department of Immunology, Hopital Europeen Georges Pompidou, Paris, France
INSERM U430 and University Paris V, Paris, France
INSERM U421, University Paris XII, Creteil, France
INSERM U421, University Paris XII, Creteil, France; Service of Clinical Immunology, Hopital Henri Mondor, Creteil, France
* Corresponding author; email: laurence.weiss{at}egp.ap-hop-paris.fr.
The present study demonstrates that CD4+CD25+ T cells, expanded in peripheral blood of HIV-infected patients receiving highly active antiretroviral therapy (HAART), exhibit phenotypic, molecular and functional characteristics of regulatory T cells. The majority of peripheral CD4+CD25+ T cells from HIV-infected patients expressed a memory phenotype. They were found to constitutively express Foxp3 messengers. CD4+CD25+ T cells weakly proliferated to immobilized anti-CD3 mAb and addition of soluble anti-CD28 mAb significantly increased proliferation. In contrast to CD4+CD25- T cells, CD4+CD25+ T cells from HIV-infected patients did not proliferate in response to recall antigens and to p24 protein. The proliferative capacity of CD4 T cells to tuberculin, CMV and p24 significantly increased following depletion of CD4+CD25+ T cells. Furthermore, addition of increasing numbers of CD4+CD25+ T cells resulted in a dose-dependent inhibition of CD4+CD25- T cell proliferation to tuberculin and p24. CD4+CD25+ T cells responded specifically to p24 antigen stimulation by expressing TGF- and IL-10, thus indicating the presence of p24-specific CD4+ T cells among the CD4+CD25+ T-cell subset. Suppressive activity was not dependent on the secretion of TGF- or IL-10. Taken together, our results suggest that persistence of HIV antigens might trigger the expansion of CD4+CD25+ regulatory T cells which might induce a tolerance to HIV in vivo.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
M. E. Moreno-Fernandez, W. Zapata, J. T. Blackard, G. Franchini, and C. A. Chougnet
Human Regulatory T Cells Are Targets for Human Immunodeficiency Virus (HIV) Infection, and Their Susceptibility Differs Depending on the HIV Type 1 Strain
J. Virol.,
December 15, 2009;
83(24):
12925 - 12933.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S Mori and P Levin
A brief review of potential mechanisms of immune reconstitution inflammatory syndrome in HIV following antiretroviral therapy
Int J STD AIDS,
July 1, 2009;
20(7):
447 - 452.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Nikolova, J.-D. Lelievre, M. Carriere, A. Bensussan, and Y. Levy
Regulatory T cells differentially modulate the maturation and apoptosis of human CD8+ T-cell subsets
Blood,
May 7, 2009;
113(19):
4556 - 4565.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Liu, N. Gong, X. Huang, A. D. Reynolds, R. L. Mosley, and H. E. Gendelman
Neuromodulatory Activities of CD4+CD25+ Regulatory T Cells in a Murine Model of HIV-1-Associated Neurodegeneration
J. Immunol.,
March 15, 2009;
182(6):
3855 - 3865.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Ji and M. W. Cloyd
HIV-1 binding to CD4 on CD4+CD25+ regulatory T cells enhances their suppressive function and induces them to home to, and accumulate in, peripheral and mucosal lymphoid tissues: an additional mechanism of immunosuppression
Int. Immunol.,
March 1, 2009;
21(3):
283 - 294.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Stevceva, V. Yoon, A. Carville, B. Pacheco, M. Santosuosso, B. Korioth-Schmitz, K. Mansfield, and M. C. Poznansky
The Efficacy of T Cell-Mediated Immune Responses Is Reduced by the Envelope Protein of the Chimeric HIV-1/SIV-KB9 Virus In Vivo
J. Immunol.,
October 15, 2008;
181(8):
5510 - 5521.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Q. Jiang, L. Zhang, R. Wang, J. Jeffrey, M. L. Washburn, D. Brouwer, S. Barbour, G. I. Kovalev, D. Unutmaz, and L. Su
FoxP3+CD4+ regulatory T cells play an important role in acute HIV-1 infection in humanized Rag2-/-{gamma}C-/- mice in vivo
Blood,
October 1, 2008;
112(7):
2858 - 2868.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. J. Chase, H.-C. Yang, H. Zhang, J. N. Blankson, and R. F. Siliciano
Preservation of FoxP3+ Regulatory T Cells in the Peripheral Blood of Human Immunodeficiency Virus Type 1-Infected Elite Suppressors Correlates with Low CD4+ T-Cell Activation
J. Virol.,
September 1, 2008;
82(17):
8307 - 8315.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Cabrera, D. Burzyn, J. Mundinano, M. C. Courreges, G. Camicia, D. Lorenzo, H. Costa, S. R. Ross, I. Nepomnaschy, and I. Piazzon
Early Increases in Superantigen-Specific Foxp3+ Regulatory T Cells during Mouse Mammary Tumor Virus Infection
J. Virol.,
August 1, 2008;
82(15):
7422 - 7431.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Gil-Guerrero, J. Dotor, I. L. Huibregtse, N. Casares, A. B. Lopez-Vazquez, F. Rudilla, J. I. Riezu-Boj, J. Lopez-Sagaseta, J. Hermida, S. Van Deventer, et al.
In Vitro and In Vivo Down-Regulation of Regulatory T Cell Activity with a Peptide Inhibitor of TGF-{beta}1
J. Immunol.,
July 1, 2008;
181(1):
126 - 135.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Cao, J. Zhao, Z. Lei, S. Shen, C. Liu, D. Li, J. Liu, G.-X. Shen, G.-M. Zhang, Z.-H. Feng, et al.
Local Accumulation of FOXP3+ Regulatory T Cells: Evidence for an Immune Evasion Mechanism in Patients with Large Condylomata Acuminata
J. Immunol.,
June 1, 2008;
180(11):
7681 - 7686.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Elrefaei, C. A. R. Baker, N. G. Jones, D. R. Bangsberg, and H. Cao
Presence of Suppressor HIV-Specific CD8+ T Cells Is Associated with Increased PD-1 Expression on Effector CD8+ T Cells
J. Immunol.,
June 1, 2008;
180(11):
7757 - 7763.
[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]
|
 |
|

|
 |

|
 |
 
V. Cecchinato, E. Tryniszewska, Z. M. Ma, M. Vaccari, A. Boasso, W.-P. Tsai, C. Petrovas, D. Fuchs, J.-M. Heraud, D. Venzon, et al.
Immune Activation Driven by CTLA-4 Blockade Augments Viral Replication at Mucosal Sites in Simian Immunodeficiency Virus Infection
J. Immunol.,
April 15, 2008;
180(8):
5439 - 5447.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. M. Dunham, B. Cervasi, J. M. Brenchley, H. Albrecht, A. Weintrob, B. Sumpter, J. Engram, S. Gordon, N. R. Klatt, I. Frank, et al.
CD127 and CD25 Expression Defines CD4+ T Cell Subsets That Are Differentially Depleted during HIV Infection
J. Immunol.,
April 15, 2008;
180(8):
5582 - 5592.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Hu, K. Fernando, H. Ni, and D. Weissman
HIV Envelope Suppresses CD4+ T Cell Activation Independent of T Regulatory Cells
J. Immunol.,
April 15, 2008;
180(8):
5593 - 5600.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. R. Van Gulck, G. Vanham, L. Heyndrickx, S. Coppens, K. Vereecken, D. Atkinson, E. Florence, I. Kint, Z. N. Berneman, and V. V. Tendeloo
Efficient In Vitro Expansion of Human Immunodeficiency Virus (HIV)-Specific T-Cell Responses by gag mRNA-Electroporated Dendritic Cells from Treated and Untreated HIV Type 1-Infected Individuals
J. Virol.,
April 1, 2008;
82(7):
3561 - 3573.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. J. Lazarus, M. A. Kay, A. L. McCarter, and R. M. Wooten
Viable Borrelia burgdorferi Enhances Interleukin-10 Production and Suppresses Activation of Murine Macrophages
Infect. Immun.,
March 1, 2008;
76(3):
1153 - 1162.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. C. Ndhlovu, C. P. Loo, G. Spotts, D. F. Nixon, and F. M. Hecht
FOXP3 expressing CD127lo CD4+ T cells inversely correlate with CD38+ CD8+ T cell activation levels in primary HIV-1 infection
J. Leukoc. Biol.,
February 1, 2008;
83(2):
254 - 262.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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]
|
 |
|

|
 |

|
 |
 
A. K. Antons, R. Wang, K. Oswald-Richter, M. Tseng, C. W. Arendt, S. A. Kalams, and D. Unutmaz
Naive Precursors of Human Regulatory T Cells Require FoxP3 for Suppression and Are Susceptible to HIV Infection
J. Immunol.,
January 15, 2008;
180(2):
764 - 773.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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]
|
 |
|

|
 |

|
 |
 
I. Karlsson, B. Malleret, P. Brochard, B. Delache, J. Calvo, R. Le Grand, and B. Vaslin
FoxP3+ CD25+ CD8+ T-Cell Induction during Primary Simian Immunodeficiency Virus Infection in Cynomolgus Macaques Correlates with Low CD4+ T-Cell Activation and High Viral Load
J. Virol.,
December 15, 2007;
81(24):
13444 - 13455.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Balkow, F. Krux, K. Loser, J. U. Becker, S. Grabbe, and U. Dittmer
Friend retrovirus infection of myeloid dendritic cells impairs maturation, prolongs contact to naive T cells, and favors expansion of regulatory T cells
Blood,
December 1, 2007;
110(12):
3949 - 3958.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Boasso, M. Vaccari, A. Hryniewicz, D. Fuchs, J. Nacsa, V. Cecchinato, J. Andersson, G. Franchini, G. M. Shearer, and C. Chougnet
Regulatory T-Cell Markers, Indoleamine 2,3-Dioxygenase, and Virus Levels in Spleen and Gut during Progressive Simian Immunodeficiency Virus Infection
J. Virol.,
November 1, 2007;
81(21):
11593 - 11603.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Holmes, G. Knudsen, S. Mackey-Cushman, and L. Su
FoxP3 Enhances HIV-1 Gene Expression by Modulating NF{kappa}B Occupancy at the Long Terminal Repeat in Human T Cells
J. Biol. Chem.,
June 1, 2007;
282(22):
15973 - 15980.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. E. Pereira, F. Villinger, N. Onlamoon, P. Bryan, A. Cardona, K. Pattanapanysat, K. Mori, S. Hagen, L. Picker, and A. A. Ansari
Simian Immunodeficiency Virus (SIV) Infection Influences the Level and Function of Regulatory T Cells in SIV-Infected Rhesus Macaques but Not SIV-Infected Sooty Mangabeys
J. Virol.,
May 1, 2007;
81(9):
4445 - 4456.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Nylen, R. Maurya, L. Eidsmo, K. D. Manandhar, S. Sundar, and D. Sacks
Splenic accumulation of IL-10 mRNA in T cells distinct from CD4+CD25+ (Foxp3) regulatory T cells in human visceral leishmaniasis
J. Exp. Med.,
April 16, 2007;
204(4):
805 - 817.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Elrefaei, F. L. Ventura, C. A. R. Baker, R. Clark, D. R. Bangsberg, and H. Cao
HIV-Specific IL-10-Positive CD8+ T Cells Suppress Cytolysis and IL-2 Production by CD8+ T Cells
J. Immunol.,
March 1, 2007;
178(5):
3265 - 3271.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Kinter, J. McNally, L. Riggin, R. Jackson, G. Roby, and A. S. Fauci
Suppression of HIV-specific T cell activity by lymph node CD25+ regulatory T cells from HIV-infected individuals
PNAS,
February 27, 2007;
104(9):
3390 - 3395.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Hryniewicz, A. Boasso, Y. Edghill-Smith, M. Vaccari, D. Fuchs, D. Venzon, J. Nacsa, M. R. Betts, W.-P. Tsai, J.-M. Heraud, et al.
CTLA-4 blockade decreases TGF-beta, IDO, and viral RNA expression in tissues of SIVmac251-infected macaques
Blood,
December 1, 2006;
108(12):
3834 - 3842.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Nilsson, A. Boasso, P. A. Velilla, R. Zhang, M. Vaccari, G. Franchini, G. M. Shearer, J. Andersson, and C. Chougnet
HIV-1-driven regulatory T-cell accumulation in lymphoid tissues is associated with disease progression in HIV/AIDS
Blood,
December 1, 2006;
108(12):
3808 - 3817.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Hosmalin and P. Lebon
Type I interferon production in HIV-infected patients
J. Leukoc. Biol.,
November 1, 2006;
80(5):
984 - 993.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H.-J. Epple, C. Loddenkemper, D. Kunkel, H. Troger, J. Maul, V. Moos, E. Berg, R. Ullrich, J.-D. Schulzke, H. Stein, et al.
Mucosal but not peripheral FOXP3+ regulatory T cells are highly increased in untreated HIV infection and normalize after suppressive HAART
Blood,
November 1, 2006;
108(9):
3072 - 3078.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. J. Zaunders, S. Ip, M. L. Munier, D. E. Kaufmann, K. Suzuki, C. Brereton, S. C. Sasson, N. Seddiki, K. Koelsch, A. Landay, et al.
Infection of CD127+ (Interleukin-7 Receptor+) CD4+ Cells and Overexpression of CTLA-4 Are Linked to Loss of Antigen-Specific CD4 T Cells during Primary Human Immunodeficiency Virus Type 1 Infection.
J. Virol.,
October 1, 2006;
80(20):
10162 - 10172.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Bourgeois and B. Stockinger
CD25+CD4+ Regulatory T Cells and Memory T Cells Prevent Lymphopenia-Induced Proliferation of Naive T Cells in Transient States of Lymphopenia
J. Immunol.,
October 1, 2006;
177(7):
4558 - 4566.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. A. Diaz and D. M. Koelle
Human CD4+ CD25high Cells Suppress Proliferative Memory Lymphocyte Responses to Herpes Simplex Virus Type 2.
J. Virol.,
August 1, 2006;
80(16):
8271 - 8273.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Xu, J. Fu, L. Jin, H. Zhang, C. Zhou, Z. Zou, J.-M. Zhao, B. Zhang, M. Shi, X. Ding, et al.
Circulating and Liver Resident CD4+CD25+ Regulatory T Cells Actively Influence the Antiviral Immune Response and Disease Progression in Patients with Hepatitis B
J. Immunol.,
July 1, 2006;
177(1):
739 - 747.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Wing, Z. Fehervari, and S. Sakaguchi
Emerging possibilities in the development and function of regulatory T cells
Int. Immunol.,
July 1, 2006;
18(7):
991 - 1000.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Schneider-Schaulies and U. Dittmer
Silencing T cells or T-cell silencing: concepts in virus-induced immunosuppression
J. Gen. Virol.,
June 1, 2006;
87(6):
1423 - 1438.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. J. Suffia, S. K. Reckling, C. A. Piccirillo, R. S. Goldszmid, and Y. Belkaid
Infected site-restricted Foxp3+ natural regulatory T cells are specific for microbial antigens
J. Exp. Med.,
March 20, 2006;
203(3):
777 - 788.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. J. Robertson, R. J. Messer, A. B. Carmody, and K. J. Hasenkrug
In Vitro Suppression of CD8+ T Cell Function by Friend Virus-Induced Regulatory T Cells
J. Immunol.,
March 15, 2006;
176(6):
3342 - 3349.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Elrefaei, B. Barugahare, F. Ssali, P. Mugyenyi, and H. Cao
HIV-Specific IL-10-Positive CD8+ T Cells Are Increased in Advanced Disease and Are Associated with Decreased HIV-Specific Cytolysis
J. Immunol.,
January 15, 2006;
176(2):
1274 - 1280.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Mesel-Lemoine, M. Cherai, S. Le Gouvello, M. Guillot, V. Leclercq, D. Klatzmann, V. Thomas-Vaslin, and F. M. Lemoine
Initial depletion of regulatory T cells: the missing solution to preserve the immune functions of T lymphocytes designed for cell therapy
Blood,
January 1, 2006;
107(1):
381 - 388.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Andersson, A. Boasso, J. Nilsson, R. Zhang, N. J. Shire, S. Lindback, G. M. Shearer, and C. A. Chougnet
Cutting Edge: The Prevalence of Regulatory T Cells in Lymphoid Tissue Is Correlated with Viral Load in HIV-Infected Patients
J. Immunol.,
March 15, 2005;
174(6):
3143 - 3147.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|