SEARCH:   Advanced

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. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-01-0365v1 104/10/3249    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Weiss, L. Articles by Levy, Y. Search for Related Content PubMed PubMed Citation Articles by Weiss, L. Articles by Levy, Y. Related Collections Immunobiology Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY 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, Michèle Balbo, Cédric Carbonneil, and Yves Levy From the Institut National de la Santé et de la Recherche Médicale (INSERM) U430 and University Paris V, Paris, France; Department of Immunology, Hôpital Européen Georges Pompidou, Paris, France; INSERM U421, Paris and University Paris XII, Créteil, France; and Service of Clinical Immunology, Hôpital Henri Mondor, Créteil, France. 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 transcription factor forkhead box P3 (Foxp3) messengers. CD4+CD25+ T cells weakly proliferated to immobilized anti-CD3 monoclonal antibody (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, cytomegalovirus (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 transforming growth factor (TGF-) and interleukin 10 (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: 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]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020