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Laboratories of
*
Immunoregulation and
Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
Science Applications International Corp., Frederick Cancer Research and Development Center, Frederick, MD 21702;
§
Emory University Vaccine Center at Yerkes, Atlanta, GA 30322; and
¶
Servicio de Medicina Interna 1, Clinica Puerta de Hierro, Universidad Autonoma de Madrid, and Servicio de Microbiologia, Hospital General Gregorio Maranon, Madrid, Spain
The virus-specific CD8+ T cell responses of 21
HIV-infected patients were studied including a unique cohort of
long-term nonprogressors with low levels of plasma viral RNA and strong
proliferative responses to HIV Ags. HIV-specific CD8+ T
cell responses were studied by a combination of standard cytotoxic T
cell (CTL) assays, MHC tetramers, and TCR repertoire analysis. The
frequencies of CD8+ T cells specific to the majority of HIV
gene products were measured by flow cytometric detection of
intracellular IFN-
in response to HIV-vaccinia recombinant-infected
autologous B cells. Very high frequencies (0.8–18.0%) of circulating
CD8+ T cells were found to be HIV specific. High
frequencies of HIV-specific CD8+ T cells were not limited
to long-tern nonprogressors with restriction of plasma virus. No
correlation was found between the frequency of HIV-specific
CD8+ T cells and levels of plasma viremia. In each case,
the vast majority of cells (up to 17.2%) responded to
gag-pol. Repertoire analysis showed these large numbers
of Ag-specific cells were scattered throughout the repertoire and in
the majority of cases not contained within large monoclonal expansions.
These data demonstrate that high numbers of HIV-specific
CD8+ T cells exist even in patients with high-level viremia
and progressive disease. Further, they suggest that other qualitative
parameters of the CD8+ T cell response may differentiate
some patients with very low levels of plasma virus and nonprogressive
disease.
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P. K. C. Goon, T. Igakura, E. Hanon, A. J. Mosley, B. Asquith, K. G. Gould, G. P. Taylor, J. N. Weber, and C. R. M. Bangham High Circulating Frequencies of Tumor Necrosis Factor Alpha- and Interleukin-2-Secreting Human T-Lymphotropic Virus Type 1 (HTLV-1)-Specific CD4+ T Cells in Patients with HTLV-1-Associated Neurological Disease J. Virol., September 1, 2003; 77(17): 9716 - 9722. [Abstract] [Full Text] [PDF]
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S. A. Migueles, A. C. Laborico, H. Imamichi, W. L. Shupert, C. Royce, M. McLaughlin, L. Ehler, J. Metcalf, S. Liu, C. W. Hallahan, et al. The Differential Ability of HLA B*5701+ Long-Term Nonprogressors and Progressors To Restrict Human Immunodeficiency Virus Replication Is Not Caused by Loss of Recognition of Autologous Viral gag Sequences J. Virol., June 15, 2003; 77(12): 6889 - 6898. [Abstract] [Full Text] [PDF]
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 M. Kano, T. Matano, A. Kato, H. Nakamura, A. Takeda, Y. Suzaki, Y. Ami, K. Terao, and Y. Nagai Primary replication of a recombinant Sendai virus vector in macaques J. Gen. Virol., June 1, 2002; 83(6): 1377 - 1386. [Abstract] [Full Text] [PDF]
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S. Kostense, K. Vandenberghe, J. Joling, D. Van Baarle, N. Nanlohy, E. Manting, and F. Miedema Persistent numbers of tetramer+ CD8+ T cells, but loss of interferon-gamma + HIV-specific T cells during progression to AIDS Blood, April 1, 2002; 99(7): 2505 - 2511. [Abstract] [Full Text] [PDF]
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D. H. Margolin, E. F. Helmuth Saunders, B. Bronfin, N. de Rosa, M. K. Axthelm, X. Alvarez, and N. L. Letvin High Frequency of Virus-Specific B Lymphocytes in Germinal Centers of Simian-Human Immunodeficiency Virus-Infected Rhesus Monkeys J. Virol., March 19, 2002; 76(8): 3965 - 3973. [Abstract] [Full Text] [PDF]
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S. Santra, J. E. Schmitz, M. J. Kuroda, M. A. Lifton, C. E. Nickerson, C. I. Lord, R. Pal, G. Franchini, and N. L. Letvin Recombinant Canarypox Vaccine-Elicited CTL Specific for Dominant and Subdominant Simian Immunodeficiency Virus Epitopes in Rhesus Monkeys J. Immunol., February 15, 2002; 168(4): 1847 - 1853. [Abstract] [Full Text] [PDF]
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M. Dybul, T.-W. Chun, C. Yoder, B. Hidalgo, M. Belson, K. Hertogs, B. Larder, R. L. Dewar, C. H. Fox, C. W. Hallahan, et al. Short-cycle structured intermittent treatment of chronic HIV infection with highly active antiretroviral therapy: Effects on virologic, immunologic, and toxicity parameters PNAS, November 29, 2001; (2001) 261568398. [Abstract] [Full Text] [PDF]
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A. C. McNeil, W. L. Shupert, C. A. Iyasere, C. W. Hallahan, J. Mican, R. T. Davey Jr., and M. Connors High-level HIV-1 viremia suppresses viral antigen-specific CD4+ T cell proliferation PNAS, November 20, 2001; 98(24): 13878 - 13883. [Abstract] [Full Text] [PDF]
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S. F. Sieg, D. A. Bazdar, C. V. Harding, and M. M. Lederman Differential Expression of Interleukin-2 and Gamma Interferon in Human Immunodeficiency Virus Disease J. Virol., October 15, 2001; 75(20): 9983 - 9985. [Abstract] [Full Text] [PDF]
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J. Lieberman, P. Shankar, N. Manjunath, and J. Andersson Dressed to kill? A review of why antiviral CD8 T lymphocytes fail to prevent progressive immunodeficiency in HIV-1 infection Blood, September 15, 2001; 98(6): 1667 - 1677. [Abstract] [Full Text] [PDF]
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 J. Wilkinson and F. Gotch Immune interventions: The changing face of HIV and AIDS Br. Med. Bull., September 1, 2001; 58(1): 187 - 203. [Abstract] [Full Text] [PDF]
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G. Chen, P. Shankar, C. Lange, H. Valdez, P. R. Skolnik, L. Wu, N. Manjunath, and J. Lieberman CD8 T cells specific for human immunodeficiency virus, Epstein-Barr virus, and cytomegalovirus lack molecules for homing to lymphoid sites of infection Blood, July 1, 2001; 98(1): 156 - 164. [Abstract] [Full Text] [PDF]
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T. U. Vogel, T. M. Allen, J. D. Altman, and D. I. Watkins Functional Impairment of Simian Immunodeficiency Virus-Specific CD8+ T Cells during the Chronic Phase of Infection J. Virol., March 1, 2001; 75(5): 2458 - 2461. [Abstract] [Full Text]
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P. A. Goepfert, A. Bansal, B. H. Edwards, G. D. Ritter Jr., I. Tellez, S. A. McPherson, S. Sabbaj, and M. J. Mulligan A Significant Number of Human Immunodeficiency Virus Epitope-Specific Cytotoxic T Lymphocytes Detected by Tetramer Binding Do Not Produce Gamma Interferon J. Virol., November 1, 2000; 74(21): 10249 - 10255. [Abstract] [Full Text]
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M. Dybul, T.-W. Chun, C. Yoder, B. Hidalgo, M. Belson, K. Hertogs, B. Larder, R. L. Dewar, C. H. Fox, C. W. Hallahan, et al. Short-cycle structured intermittent treatment of chronic HIV infection with highly active antiretroviral therapy: Effects on virologic, immunologic, and toxicity parameters PNAS, December 18, 2001; 98(26): 15161 - 15166. [Abstract] [Full Text] [PDF]
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