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Science 21 November 1997:
Vol. 278. no. 5342, pp. 1447 - 1450
DOI: 10.1126/science.278.5342.1447
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Vigorous HIV-1-Specific CD4+ T Cell Responses Associated with Control of Viremia

Eric S. Rosenberg, James M. Billingsley, Angela M. Caliendo, Steven L. Boswell, Paul E. Sax, Spyros A. Kalams, Bruce D. Walker *

Virus-specific CD4+ T helper lymphocytes are critical to the maintenance of effective immunity in a number of chronic viral infections, but are characteristically undetectable in chronic human immunodeficiency virus-type 1 (HIV-1) infection. In individuals who control viremia in the absence of antiviral therapy, polyclonal, persistent, and vigorous HIV-1-specific CD4+ T cell proliferative responses were present, resulting in the elaboration of interferon-gamma and antiviral beta  chemokines. In persons with chronic infection, HIV-1-specific proliferative responses to p24 were inversely related to viral load. Strong HIV-1-specific proliferative responses were also detected following treatment of acutely infected persons with potent antiviral therapy. The HIV-1-specific helper cells are likely to be important in immunotherapeutic interventions and vaccine development.

E. S. Rosenberg, J. M. Billingsley, S. A. Kalams, B. D. Walker, Partners AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, and Harvard Medical School, Boston, MA 02114, USA.
A. M. Caliendo, Partners AIDS Research Center and Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
S. L. Boswell, Fenway Community Health Center, Boston, MA 02115, USA.
P. E. Sax, Partners AIDS Research Center and Division of Infectious Diseases, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
*   To whom correspondence should be addressed. E-mail: bwalker{at}helix.mgh.harvard.edu

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Broad Repertoire of the CD4+ Th Cell Response in Spontaneously Controlled Hepatitis C Virus Infection Includes Dominant and Highly Promiscuous Epitopes.
J. Schulze zur Wiesch, G. M. Lauer, C. L. Day, A. Y. Kim, K. Ouchi, J. E. Duncan, A. G. Wurcel, J. Timm, A. M. Jones, B. Mothe, et al. (2005)
J. Immunol. 175, 3603-3613
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Major Histocompatibility Complex Class II (HLA-DRB and -DQB) Allele Frequencies in Botswana: Association with Human Immunodeficiency Virus Type 1 Infection.
T. Ndung'u, S. Gaseitsiwe, E. Sepako, F. Doualla-Bell, T. Peter, S. Kim, I. Thior, V. A. Novitsky, and M. Essex (2005)
Clin. Vaccine Immunol. 12, 1020-1028
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Early proliferation of CCR5+ CD38+++ antigen-specific CD4+ Th1 effector cells during primary HIV-1 infection.
J. J. Zaunders, M. L. Munier, D. E. Kaufmann, S. Ip, P. Grey, D. Smith, T. Ramacciotti, D. Quan, R. Finlayson, J. Kaldor, et al. (2005)
Blood 106, 1660-1667
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Intrinsic Functional Dysregulation of CD4 T Cells Occurs Rapidly following Persistent Viral Infection.
D. G. Brooks, L. Teyton, M. B. A. Oldstone, and D. B. McGavern (2005)
J. Virol. 79, 10514-10527
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A Soluble Factor Secreted by an HIV-1-Resistant Cell Line Blocks Transcription through Inactivating the DNA-Binding Capacity of the NF-{kappa}B p65/p50 Dimer.
A. Lesner, Y. Li, J. Nitkiewicz, G. Li, A. Kartvelishvili, M. Kartvelishvili, and M. Simm (2005)
J. Immunol. 175, 2548-2554
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Lymphocyte Proliferation Responses Induced to Broadly Reactive Th Peptides Did Not Protect against Equine Infectious Anemia Virus Challenge.
D. G. Fraser, S. R. Leib, B. S. Zhang, R. H. Mealey, W. C. Brown, and T. C. McGuire (2005)
Clin. Vaccine Immunol. 12, 983-993
   Abstract »    Full Text »    PDF »
Reconstitution of EBV Latent but Not Lytic Antigen-Specific CD4+ and CD8+ T Cells after HIV Treatment with Highly Active Antiretroviral Therapy.
E. Piriou, C. A. Jansen, K. v. Dort, I. De Cuyper, N. M. Nanlohy, J. M. A. Lange, M. H. J. van Oers, F. Miedema, and D. van Baarle (2005)
J. Immunol. 175, 2010-2017
   Abstract »    Full Text »    PDF »
Immunization of Macaques with Single-Cycle Simian Immunodeficiency Virus (SIV) Stimulates Diverse Virus-Specific Immune Responses and Reduces Viral Loads after Challenge with SIVmac239.
D. T. Evans, J. E. Bricker, H. B. Sanford, S. Lang, A. Carville, B. A. Richardson, M. Piatak Jr., J. D. Lifson, K. G. Mansfield, and R. C. Desrosiers (2005)
J. Virol. 79, 7707-7720
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Induction of T-Cell Immunity to Antiretroviral Drug-Resistant Human Immunodeficiency Virus Type 1.
I. Stratov, C. J. Dale, S. Chea, J. McCluskey, and S. J. Kent (2005)
J. Virol. 79, 7728-7737
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Correlates of Delayed Disease Progression in HIV-1-Infected Kenyan Children.
R. Chakraborty, A.-S. Morel, J. K. Sutton, V. Appay, R. M. Ripley, T. Dong, T. Rostron, S. Ogola, T. Palakudy, R. Musoke, et al. (2005)
J. Immunol. 174, 8191-8199
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CD8+ T Cell Dynamics during Primary Simian Immunodeficiency Virus Infection in Macaques: Relationship of Effector Cell Differentiation with the Extent of Viral Replication.
V. Monceaux, L. Viollet, F. Petit, R. H. T. Fang, M.-C. Cumont, J. Zaunders, B. Hurtrel, and J. Estaquier (2005)
J. Immunol. 174, 6898-6908
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A critical role of T cell antigen receptor-transduced MHC class I-restricted helper T cells in tumor protection.
E. C. Morris, A. Tsallios, G. M. Bendle, S.-a. Xue, and H. J. Stauss (2005)
PNAS 102, 7934-7939
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Enhanced Cellular Immunity in Macaques following a Novel Peptide Immunotherapy.
S. Chea, C. J. Dale, R. De Rose, I. A. Ramshaw, and S. J. Kent (2005)
J. Virol. 79, 3748-3757
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Cutting Edge: The Prevalence of Regulatory T Cells in Lymphoid Tissue Is Correlated with Viral Load in HIV-Infected Patients.
J. Andersson, A. Boasso, J. Nilsson, R. Zhang, N. J. Shire, S. Lindback, G. M. Shearer, and C. A. Chougnet (2005)
J. Immunol. 174, 3143-3147
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A Statistical Characterization of Consistent Patterns of Human Immunodeficiency Virus Evolution Within Infected Patients.
S. Williamson, S. M. Perry, C. D. Bustamante, M. E. Orive, M. N. Stearns, and J. K. Kelly (2005)
Mol. Biol. Evol. 22, 456-468
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Preferential Apoptosis of HIV-1-Specific CD4+ T Cells.
F. Y. Yue, C. M. Kovacs, R. C. Dimayuga, X. X. J. Gu, P. Parks, R. Kaul, and M. A. Ostrowski (2005)
J. Immunol. 174, 2196-2204
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Contribution of Virus-Like Particles to the Immunogenicity of Human Immunodeficiency Virus Type 1 Gag-Derived Vaccines in Mice.
S. B. J. Wong and R. F. Siliciano (2005)
J. Virol. 79, 1701-1712
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Memory Responses in Human Immunodeficiency Virus Type 1-Infected Individuals with Long-Term Viral Load Suppression Are Independent of CD4 Cell Nadir.
M. A. Kolber, M. O. Saenz, and S. Kaul (2005)
Clin. Vaccine Immunol. 12, 76-80
   Abstract »    Full Text »    PDF »
HIV-specific Cytotoxic T Cells from Long-Term Survivors Select a Unique T Cell Receptor.
T. Dong, G. Stewart-Jones, N. Chen, P. Easterbrook, X. Xu, L. Papagno, V. Appay, M. Weekes, C. Conlon, C. Spina, et al. (2004)
J. Exp. Med. 200, 1547-1557
   Abstract »    Full Text »    PDF »
Comparison of Human Immunodeficiency Virus (HIV)-Specific T-Cell Responses in HIV-1- and HIV-2-Infected Individuals in Senegal.
N. N. Zheng, N. B. Kiviat, P. S. Sow, S. E. Hawes, A. Wilson, H. Diallo-Agne, C. W. Critchlow, G. S. Gottlieb, L. Musey, and M. J. McElrath (2004)
J. Virol. 78, 13934-13942
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Human immunodeficiency virus-driven expansion of CD4+CD25+ regulatory T cells, which suppress HIV-specific CD4 T-cell responses in HIV-infected patients.
L. Weiss, V. Donkova-Petrini, L. Caccavelli, M. Balbo, C. Carbonneil, and Y. Levy (2004)
Blood 104, 3249-3256
   Abstract »    Full Text »    PDF »
Impact of Immune Plasticity on Development of Cellular Memory Responses to Human Immunodeficiency Virus Type 1.
M. A. Kolber (2004)
Clin. Vaccine Immunol. 11, 1002-1007
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Recall antigen activation induces prompt release of CCR5 ligands from PBMC: implication in memory responses and immunization.
L. Sun, S. F. Abdelwahab, G. K. Lewis, and A. Garzino-Demo (2004)
Int. Immunol. 16, 1623-1631
   Abstract »    Full Text »    PDF »
Human Immunodeficiency Virus Type 1 Gag-Specific Mucosal Immunity after Oral Immunization with Papillomavirus Pseudoviruses Encoding Gag.
H. Zhang, R. Fayad, X. Wang, D. Quinn, and L. Qiao (2004)
J. Virol. 78, 10249-10257
   Abstract »    Full Text »    PDF »
Comprehensive Analysis of Nef Functions Selected in Simian Immunodeficiency Virus-Infected Macaques.
M. Schindler, J. Munch, M. Brenner, C. Stahl-Hennig, J. Skowronski, and F. Kirchhoff (2004)
J. Virol. 78, 10588-10597
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Loss of HIV-1-specific CD8+ T Cell Proliferation after Acute HIV-1 Infection and Restoration by Vaccine-induced HIV-1-specific CD4+ T Cells.
M. Lichterfeld, D. E. Kaufmann, X. G. Yu, S. K. Mui, M. M. Addo, M. N. Johnston, D. Cohen, G. K. Robbins, E. Pae, G. Alter, et al. (2004)
J. Exp. Med. 200, 701-712
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A Consecutive Priming-Boosting Vaccination of Mice with Simian Immunodeficiency Virus (SIV) gag/pol DNA and Recombinant Vaccinia Virus Strain DIs Elicits Effective Anti-SIV Immunity.
K. Someya, K.-Q. Xin, K. Matsuo, K. Okuda, N. Yamamoto, and M. Honda (2004)
J. Virol. 78, 9842-9853
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A prospective study demonstrates an association between JC virus-specific cytotoxic T lymphocytes and the early control of progressive multifocal leukoencephalopathy.
R. A. Du Pasquier, M. J. Kuroda, Y. Zheng, J. Jean-Jacques, N. L. Letvin, and I. J. Koralnik (2004)
Brain 127, 1970-1978
   Abstract »    Full Text »    PDF »
Beyond Help: Direct Effector Functions of Human Immunodeficiency Virus Type 1-Specific CD4+ T Cells.
P. J. Norris, H. F. Moffett, O. O. Yang, D. E. Kaufmann, M. J. Clark, M. M. Addo, and E. S. Rosenberg (2004)
J. Virol. 78, 8844-8851
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