Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 1922K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kinter, A. L. Articles by Fauci, A. S. Search for Related Content PubMed PubMed Citation Articles by Kinter, A. L. Articles by Fauci, A. S. Pubmed/NCBI databases Substance via MeSH Social Bookmarking                      What's this?

¹ Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases and ² Department of Clinical Center Medicine, National Institutes of Health, Bethesda, MD 20892
³ Benaroya Research Institute, Virginia Mason Medical Center, Seattle, WA 98111

Address correspondence to Audrey L. Kinter, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, 10 Center Dr., Bldg. 10, Rm. 6A33, MSC-1576, Bethesda, MD 20892. Phone: (301) 496-7590; Fax: (301) 402-4122; email: AKinter{at}niaid.nih.gov

Human immunodeficiency virus (HIV) disease is associated with loss of CD4⁺ T cells, chronic immune activation, and progressive immune dysfunction. HIV-specific responses, particularly those of CD4⁺ T cells, become impaired early after infection, before the loss of responses directed against other antigens; the basis for this diminution has not been elucidated fully. The potential role of CD25⁺CD4⁺ regulatory T cells (T reg cells), previously shown to inhibit immune responses directed against numerous pathogens, as suppressors of HIV-specific T cell responses was investigated. In the majority of healthy HIV-infected individuals, CD25⁺CD4⁺ T cells significantly suppressed cellular proliferation and cytokine production by CD4⁺ and CD8⁺ T cells in response to HIV antigens/peptides in vitro; these effects were cell contact dependent and IL-10 and TGF-ß independent. Individuals with strong HIV-specific CD25⁺ T reg cell function in vitro had significantly lower levels of plasma viremia and higher CD4⁺: CD8⁺ T cell ratios than did those individuals in whom this activity could not be detected. These in vitro data suggest that CD25⁺CD4⁺ T reg cells may contribute to the diminution of HIV-specific T cell immune responses in vivo in the early stages of HIV disease.

Key Words: cytokine • proliferation • human • suppression • FoxP3

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Nikolova, M., Lelievre, J.-D., Carriere, M., Bensussan, A., Levy, Y. (2009). Regulatory T cells differentially modulate the maturation and apoptosis of human CD8+ T-cell subsets. Blood 113: 4556-4565 [Abstract] [Full Text]  
• Koopman, G., Mortier, D., Hofman, S., Koutsoukos, M., Bogers, W. M. J. M., Wahren, B., Voss, G., Heeney, J. L. (2009). Acute-phase CD4+ T-cell proliferation and CD152 upregulation predict set-point virus replication in vaccinated simian-human immunodeficiency virus strain 89.6p-infected macaques. J. Gen. Virol. 90: 915-926 [Abstract] [Full Text]  
• Liu, J., Gong, N., Huang, X., Reynolds, A. D., Mosley, R. L., Gendelman, H. E. (2009). Neuromodulatory Activities of CD4+CD25+ Regulatory T Cells in a Murine Model of HIV-1-Associated Neurodegeneration. J. Immunol. 182: 3855-3865 [Abstract] [Full Text]  
• Ji, J., Cloyd, M. W. (2009). 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 21: 283-294 [Abstract] [Full Text]  
• Stevceva, L., Yoon, V., Carville, A., Pacheco, B., Santosuosso, M., Korioth-Schmitz, B., Mansfield, K., Poznansky, M. C. (2008). 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. 181: 5510-5521 [Abstract] [Full Text]  
• Feske, M., Nudelman, R. J., Medina, M., Lew, J., Singh, M., Couturier, J., Graviss, E. A., Lewis, D. E. (2008). Enhancement of Human Antigen-Specific Memory T-Cell Responses by Interleukin-7 May Improve Accuracy in Diagnosing Tuberculosis. CVI 15: 1616-1622 [Abstract] [Full Text]  
• Jiang, Q., Zhang, L., Wang, R., Jeffrey, J., Washburn, M. L., Brouwer, D., Barbour, S., Kovalev, G. I., Unutmaz, D., Su, L. (2008). FoxP3+CD4+ regulatory T cells play an important role in acute HIV-1 infection in humanized Rag2-/-{gamma}C-/- mice in vivo. Blood 112: 2858-2868 [Abstract] [Full Text]  
• Chase, A. J., Yang, H.-C., Zhang, H., Blankson, J. N., Siliciano, R. F. (2008). 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. 82: 8307-8315 [Abstract] [Full Text]  
• Gil-Guerrero, L., Dotor, J., Huibregtse, I. L., Casares, N., Lopez-Vazquez, A. B., Rudilla, F., Riezu-Boj, J. I., Lopez-Sagaseta, J., Hermida, J., Van Deventer, S., Bezunartea, J., Llopiz, D., Sarobe, P., Prieto, J., Borras-Cuesta, F., Lasarte, J. J. (2008). In Vitro and In Vivo Down-Regulation of Regulatory T Cell Activity with a Peptide Inhibitor of TGF-{beta}1. J. Immunol. 181: 126-135 [Abstract] [Full Text]  
• Elrefaei, M., Baker, C. A. R., Jones, N. G., Bangsberg, D. R., Cao, H. (2008). Presence of Suppressor HIV-Specific CD8+ T Cells Is Associated with Increased PD-1 Expression on Effector CD8+ T Cells. J. Immunol. 180: 7757-7763 [Abstract] [Full Text]  
• Cecchinato, V., Tryniszewska, E., Ma, Z. M., Vaccari, M., Boasso, A., Tsai, W.-P., Petrovas, C., Fuchs, D., Heraud, J.-M., Venzon, D., Shearer, G. M., Koup, R. A., Lowy, I., Miller, C. J., Franchini, G. (2008). Immune Activation Driven by CTLA-4 Blockade Augments Viral Replication at Mucosal Sites in Simian Immunodeficiency Virus Infection. J. Immunol. 180: 5439-5447 [Abstract] [Full Text]  
• Dunham, R. M., Cervasi, B., Brenchley, J. M., Albrecht, H., Weintrob, A., Sumpter, B., Engram, J., Gordon, S., Klatt, N. R., Frank, I., Sodora, D. L., Douek, D. C., Paiardini, M., Silvestri, G. (2008). CD127 and CD25 Expression Defines CD4+ T Cell Subsets That Are Differentially Depleted during HIV Infection. J. Immunol. 180: 5582-5592 [Abstract] [Full Text]  
• Hu, H., Fernando, K., Ni, H., Weissman, D. (2008). HIV Envelope Suppresses CD4+ T Cell Activation Independent of T Regulatory Cells. J. Immunol. 180: 5593-5600 [Abstract] [Full Text]  
• Ndhlovu, L. C., Loo, C. P., Spotts, G., Nixon, D. F., Hecht, F. M. (2008). FOXP3 expressing CD127lo CD4+ T cells inversely correlate with CD38+ CD8+ T cell activation levels in primary HIV-1 infection. J. Leukoc. Biol. 83: 254-262 [Abstract] [Full Text]  
• Roy, S., Barnes, P. F., Garg, A., Wu, S., Cosman, D., Vankayalapati, R. (2008). NK Cells Lyse T Regulatory Cells That Expand in Response to an Intracellular Pathogen. J. Immunol. 180: 1729-1736 [Abstract] [Full Text]  
• Antons, A. K., Wang, R., Oswald-Richter, K., Tseng, M., Arendt, C. W., Kalams, S. A., Unutmaz, D. (2008). Naive Precursors of Human Regulatory T Cells Require FoxP3 for Suppression and Are Susceptible to HIV Infection. J. Immunol. 180: 764-773 [Abstract] [Full Text]  
• Li, S., Gowans, E. J., Chougnet, C., Plebanski, M., Dittmer, U. (2008). Natural Regulatory T Cells and Persistent Viral Infection. J. Virol. 82: 21-30 [Full Text]  
• Karlsson, I., Malleret, B., Brochard, P., Delache, B., Calvo, J., Le Grand, R., Vaslin, B. (2007). 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. 81: 13444-13455 [Abstract] [Full Text]  
• Chase, A. J., Sedaghat, A. R., German, J. R., Gama, L., Zink, M. C., Clements, J. E., Siliciano, R. F. (2007). Severe Depletion of CD4+ CD25+ Regulatory T Cells from the Intestinal Lamina Propria but Not Peripheral Blood or Lymph Nodes during Acute Simian Immunodeficiency Virus Infection. J. Virol. 81: 12748-12757 [Abstract] [Full Text]  
• Balkow, S., Krux, F., Loser, K., Becker, J. U., Grabbe, S., Dittmer, U. (2007). Friend retrovirus infection of myeloid dendritic cells impairs maturation, prolongs contact to naive T cells, and favors expansion of regulatory T cells. Blood 110: 3949-3958 [Abstract] [Full Text]  
• Boasso, A., Vaccari, M., Hryniewicz, A., Fuchs, D., Nacsa, J., Cecchinato, V., Andersson, J., Franchini, G., Shearer, G. M., Chougnet, C. (2007). Regulatory T-Cell Markers, Indoleamine 2,3-Dioxygenase, and Virus Levels in Spleen and Gut during Progressive Simian Immunodeficiency Virus Infection. J. Virol. 81: 11593-11603 [Abstract] [Full Text]  
• Hougardy, J.-M., Place, S., Hildebrand, M., Drowart, A., Debrie, A.-S., Locht, C., Mascart, F. (2007). Regulatory T Cells Depress Immune Responses to Protective Antigens in Active Tuberculosis. Am. J. Respir. Crit. Care Med. 176: 409-416 [Abstract] [Full Text]  
• Nesburn, A. B., Bettahi, I., Dasgupta, G., Chentoufi, A. A., Zhang, X., You, S., Morishige, N., Wahlert, A. J., Brown, D. J., Jester, J. V., Wechsler, S. L., BenMohamed, L. (2007). Functional Foxp3+ CD4+ CD25(Bright+) "Natural" Regulatory T Cells Are Abundant in Rabbit Conjunctiva and Suppress Virus-Specific CD4+ and CD8+ Effector T Cells during Ocular Herpes Infection. J. Virol. 81: 7647-7661 [Abstract] [Full Text]  
• Holmes, D., Knudsen, G., Mackey-Cushman, S., Su, L. (2007). FoxP3 Enhances HIV-1 Gene Expression by Modulating NF{kappa}B Occupancy at the Long Terminal Repeat in Human T Cells. J. Biol. Chem. 282: 15973-15980 [Abstract] [Full Text]  
• Pereira, L. E., Villinger, F., Onlamoon, N., Bryan, P., Cardona, A., Pattanapanysat, K., Mori, K., Hagen, S., Picker, L., Ansari, A. A. (2007). 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. 81: 4445-4456 [Abstract] [Full Text]  
• Nylen, S., Maurya, R., Eidsmo, L., Manandhar, K. D., Sundar, S., Sacks, D. (2007). Splenic accumulation of IL-10 mRNA in T cells distinct from CD4+CD25+ (Foxp3) regulatory T cells in human visceral leishmaniasis. JEM 204: 805-817 [Abstract] [Full Text]  
• Elrefaei, M., Ventura, F. L., Baker, C. A. R., Clark, R., Bangsberg, D. R., Cao, H. (2007). HIV-Specific IL-10-Positive CD8+ T Cells Suppress Cytolysis and IL-2 Production by CD8+ T Cells. J. Immunol. 178: 3265-3271 [Abstract] [Full Text]  
• Kinter, A., McNally, J., Riggin, L., Jackson, R., Roby, G., Fauci, A. S. (2007). Suppression of HIV-specific T cell activity by lymph node CD25+ regulatory T cells from HIV-infected individuals. Proc. Natl. Acad. Sci. USA 104: 3390-3395 [Abstract] [Full Text]  
• Hryniewicz, A., Boasso, A., Edghill-Smith, Y., Vaccari, M., Fuchs, D., Venzon, D., Nacsa, J., Betts, M. R., Tsai, W.-P., Heraud, J.-M., Beer, B., Blanset, D., Chougnet, C., Lowy, I., Shearer, G. M., Franchini, G. (2006). CTLA-4 blockade decreases TGF-beta, IDO, and viral RNA expression in tissues of SIVmac251-infected macaques. Blood 108: 3834-3842 [Abstract] [Full Text]  
• Nilsson, J., Boasso, A., Velilla, P. A., Zhang, R., Vaccari, M., Franchini, G., Shearer, G. M., Andersson, J., Chougnet, C. (2006). HIV-1-driven regulatory T-cell accumulation in lymphoid tissues is associated with disease progression in HIV/AIDS. Blood 108: 3808-3817 [Abstract] [Full Text]  
• Hosmalin, A., Lebon, P. (2006). Type I interferon production in HIV-infected patients. J. Leukoc. Biol. 80: 984-993 [Abstract] [Full Text]  
• Epple, H.-J., Loddenkemper, C., Kunkel, D., Troger, H., Maul, J., Moos, V., Berg, E., Ullrich, R., Schulzke, J.-D., Stein, H., Duchmann, R., Zeitz, M., Schneider, T. (2006). Mucosal but not peripheral FOXP3+ regulatory T cells are highly increased in untreated HIV infection and normalize after suppressive HAART. Blood 108: 3072-3078 [Abstract] [Full Text]  
• Zaunders, J. J., Ip, S., Munier, M. L., Kaufmann, D. E., Suzuki, K., Brereton, C., Sasson, S. C., Seddiki, N., Koelsch, K., Landay, A., Grey, P., Finlayson, R., Kaldor, J., Rosenberg, E. S., Walker, B. D., Fazekas de St. Groth, B., Cooper, D. A., Kelleher, A. D., on Behalf of the PHAEDRA Study Team, (2006). 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. 80: 10162-10172 [Abstract] [Full Text]  
• Delobel, P., Nugeyre, M.-T., Cazabat, M., Sandres-Saune, K., Pasquier, C., Cuzin, L., Marchou, B., Massip, P., Cheynier, R., Barre-Sinoussi, F., Izopet, J., Israel, N. (2006). Naive T-cell depletion related to infection by x4 human immunodeficiency virus type 1 in poor immunological responders to highly active antiretroviral therapy.. J. Virol. 80: 10229-10236 [Abstract] [Full Text]  
• Gandhi, M. K., Lambley, E., Duraiswamy, J., Dua, U., Smith, C., Elliott, S., Gill, D., Marlton, P., Seymour, J., Khanna, R. (2006). 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 108: 2280-2289 [Abstract] [Full Text]  
• Wei, S., Kryczek, I., Zou, W. (2006). Regulatory T-cell compartmentalization and trafficking. Blood 108: 426-431 [Abstract] [Full Text]  
• Xu, D., Fu, J., Jin, L., Zhang, H., Zhou, C., Zou, Z., Zhao, J.-M., Zhang, B., Shi, M., Ding, X., Tang, Z., Fu, Y.-X., Wang, F.-S. (2006). 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. 177: 739-747 [Abstract] [Full Text]  
• Schneider-Schaulies, S., Dittmer, U. (2006). Silencing T cells or T-cell silencing: concepts in virus-induced immunosuppression. J. Gen. Virol. 87: 1423-1438 [Abstract] [Full Text]  
• Vojdani, A., Erde, J. (2006). Regulatory T Cells, a Potent Immunoregulatory Target for CAM Researchers: Modulating Allergic and Infectious Disease Pathology (II). Evid Based Complement Alternat Med 3: 209-215 [Abstract] [Full Text]  
• Guyot-Revol, V., Innes, J. A., Hackforth, S., Hinks, T., Lalvani, A. (2006). Regulatory T Cells Are Expanded in Blood and Disease Sites in Patients with Tuberculosis. Am. J. Respir. Crit. Care Med. 173: 803-810 [Abstract] [Full Text]  
• Suffia, I. J., Reckling, S. K., Piccirillo, C. A., Goldszmid, R. S., Belkaid, Y. (2006). Infected site-restricted Foxp3+ natural regulatory T cells are specific for microbial antigens. JEM 203: 777-788 [Abstract] [Full Text]  
• Robertson, S. J., Messer, R. J., Carmody, A. B., Hasenkrug, K. J. (2006). In Vitro Suppression of CD8+ T Cell Function by Friend Virus-Induced Regulatory T Cells. J. Immunol. 176: 3342-3349 [Abstract] [Full Text]  
• Kornbluth, R. S. (2006). HIV creates an immunologic black hole. Blood 107: 1743-1744 [Full Text]  
• Yu, Q., Yue, F. Y., Gu, X. X., Schwartz, H., Kovacs, C. M., Ostrowski, M. A. (2006). OX40 Ligation of CD4+ T Cells Enhances Virus-Specific CD8+ T Cell Memory Responses Independently of IL-2 and CD4+ T Regulatory Cell Inhibition. J. Immunol. 176: 2486-2495 [Abstract] [Full Text]  
• Elrefaei, M., Barugahare, B., Ssali, F., Mugyenyi, P., Cao, H. (2006). HIV-Specific IL-10-Positive CD8+ T Cells Are Increased in Advanced Disease and Are Associated with Decreased HIV-Specific Cytolysis. J. Immunol. 176: 1274-1280 [Abstract] [Full Text]  
• Mesel-Lemoine, M., Cherai, M., Le Gouvello, S., Guillot, M., Leclercq, V., Klatzmann, D., Thomas-Vaslin, V., Lemoine, F. M. (2006). Initial depletion of regulatory T cells: the missing solution to preserve the immune functions of T lymphocytes designed for cell therapy. Blood 107: 381-388 [Abstract] [Full Text]  
• Karlsson, I., Grivel, J.-C., Chen, S. S., Karlsson, A., Albert, J., Fenyo, E. M., Margolis, L. B. (2005). Differential Pathogenesis of Primary CCR5-Using Human Immunodeficiency Virus Type 1 Isolates in Ex Vivo Human Lymphoid Tissue. J. Virol. 79: 11151-11160 [Abstract] [Full Text]  
• Evans, D. T., Bricker, J. E., Sanford, H. B., Lang, S., Carville, A., Richardson, B. A., Piatak, M. Jr., Lifson, J. D., Mansfield, K. G., Desrosiers, R. C. (2005). Immunization of Macaques with Single-Cycle Simian Immunodeficiency Virus (SIV) Stimulates Diverse Virus-Specific Immune Responses and Reduces Viral Loads after Challenge with SIVmac239. J. Virol. 79: 7707-7720 [Abstract] [Full Text]  
• Boettler, T., Spangenberg, H. C., Neumann-Haefelin, C., Panther, E., Urbani, S., Ferrari, C., Blum, H. E., von Weizsacker, F., Thimme, R. (2005). T Cells with a CD4+CD25+ Regulatory Phenotype Suppress In Vitro Proliferation of Virus-Specific CD8+ T Cells during Chronic Hepatitis C Virus Infection. J. Virol. 79: 7860-7867 [Abstract] [Full Text]  
• Koenen, H. J. P. M., Fasse, E., Joosten, I. (2005). CD27/CFSE-Based Ex Vivo Selection of Highly Suppressive Alloantigen-Specific Human Regulatory T Cells. J. Immunol. 174: 7573-7583 [Abstract] [Full Text]  
• McElroy, M. D., Elrefaei, M., Jones, N., Ssali, F., Mugyenyi, P., Barugahare, B., Cao, H. (2005). Coinfection with Schistosoma mansoni Is Associated with Decreased HIV-Specific Cytolysis and Increased IL-10 Production. J. Immunol. 174: 5119-5123 [Abstract] [Full Text]  
• Marchetti, G., Franzetti, F., Gori, A. (2005). Partial immune reconstitution following highly active antiretroviral therapy: can adjuvant interleukin-2 fill the gap?. J Antimicrob Chemother 55: 401-409 [Abstract] [Full Text]  
• Eggena, M. P., Barugahare, B., Jones, N., Okello, M., Mutalya, S., Kityo, C., Mugyenyi, P., Cao, H. (2005). Depletion of Regulatory T Cells in HIV Infection Is Associated with Immune Activation. J. Immunol. 174: 4407-4414 [Abstract] [Full Text]  
• Andersson, J., Boasso, A., Nilsson, J., Zhang, R., Shire, N. J., Lindback, S., Shearer, G. M., Chougnet, C. A. (2005). Cutting Edge: The Prevalence of Regulatory T Cells in Lymphoid Tissue Is Correlated with Viral Load in HIV-Infected Patients. J. Immunol. 174: 3143-3147 [Abstract] [Full Text]  
• Nacsa, J., Edghill-Smith, Y., Tsai, W.-P., Venzon, D., Tryniszewska, E., Hryniewicz, A., Moniuszko, M., Kinter, A., Smith, K. A., Franchini, G. (2005). Contrasting Effects of Low-Dose IL-2 on Vaccine-Boosted Simian Immunodeficiency Virus (SIV)-Specific CD4+ and CD8+ T Cells in Macaques Chronically Infected with SIVmac251. J. Immunol. 174: 1913-1921 [Abstract] [Full Text]  
• (2004). Regulatory T Cells: Protective Tolerance of HIV Infection?. AIDS Clin Care 2004: 8-8 [Full Text]  
• Baecher-Allan, C., Hafler, D. A. (2004). Suppressor T Cells in Human Diseases. JEM 200: 273-276 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS