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,
*
Center for AIDS Research, Division of Infectious Diseases and Geographic Medicine, Stanford University Medical Center, Stanford, CA 94305;
Department of Microbiology and Immunology and Howard Hughes Institute, Stanford University, Stanford, CA 94305; and
Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322
Peptide/MHC tetrameric complexes were used to enumerate the frequency of HLA class I-restricted epitope-specific CD8+ T cells in 18 HLA-A*0201 HIV type 1-infected asymptomatic patients. HLA-A*0201 molecules were complexed to HIV Gag p17 (amino acids 77–85) and reverse transcriptase (amino acids 464–472) peptides, biotinylated, and bound to streptavidin-phycoerythrin to form tetramers. We show in this study that 17 of 18 HIV-1-infected asymptomatic patients have circulating frequencies of 1/50–1/1000 CD8+ T cells that recognize both Gag and Pol CTL epitopes or either epitope alone. The functional nature of these cells is open to interpretation, as we show that despite relatively high frequencies of fresh epitope-specific CD8+ T cells, variant epitope sequences in viral plasma progeny were rare. In addition, the majority of tetramer-positive cells did not display discernible fresh CTL activity; only after restimulation with specific peptide in culture was there an expansion of epitope-specific CD8+ cells, correlating with high CTL activity. These data suggest that fresh tetramer-stained cells probably represent memory precursors; we demonstrate, with the application of highly active antiretroviral therapy, that the interruption of chronic antigenic stimulation causes significant reductions in the frequency of these cells in five of six patients. In conclusion, this study provides evidence that persistently replicating viral populations are probably required to maintain high frequencies of HIV-1 epitope-specific CD8+ T cells in asymptomatic chronically infected individuals
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D. Wodarz, R. M. May, and M. A. Nowak The role of antigen-independent persistence of memory cytotoxic T lymphocytes Int. Immunol., April 1, 2000; 12(4): 467 - 477. [Abstract] [Full Text] [PDF]
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A. Oxenius, D. A. Price, P. J. Easterbrook, C. A. O'Callaghan, A. D. Kelleher, J. A. Whelan, G. Sontag, A. K. Sewell, and R. E. Phillips Early highly active antiretroviral therapy for acute HIV-1 infection preserves immune function of CD8+ and CD4+ T lymphocytes PNAS, March 28, 2000; 97(7): 3382 - 3387. [Abstract] [Full Text] [PDF]
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 P. R Smith, J. D Cavenagh, T. Milne, D. Howe, S. J Wilkes, P. Sinnott, G. E Forster, and M. Helbert Benign monoclonal expansion of CD8+ lymphocytes in HIV infection J. Clin. Pathol., March 1, 2000; 53(3): 177 - 181. [Abstract] [Full Text] [PDF]
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H. Soudeyns, G. Campi, G. P. Rizzardi, C. Lenge, J. F. Demarest, G. Tambussi, A. Lazzarin, D. Kaufmann, G. Casorati, L. Corey, et al. Initiation of antiretroviral therapy during primary HIV-1 infection induces rapid stabilization of the T-cell receptor beta chain repertoire and reduces the level of T-cell oligoclonality Blood, March 1, 2000; 95(5): 1743 - 1751. [Abstract] [Full Text] [PDF]
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H. M. L. Spiegel, G. S. Ogg, E. DeFalcon, M. E. Sheehy, S. Monard, P. A. J. Haslett, G. Gillespie, S. M. Donahoe, H. Pollack, W. Borkowsky, et al. Human Immunodeficiency Virus Type 1- and Cytomegalovirus-Specific Cytotoxic T Lymphocytes Can Persist at High Frequency for Prolonged Periods in the Absence of Circulating Peripheral CD4+ T Cells J. Virol., January 1, 2000; 74(2): 1018 - 1022. [Abstract] [Full Text]
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D. Wodarz and M. A. Nowak Specific therapy regimes could lead to long-term immunological control of HIV PNAS, December 7, 1999; 96(25): 14464 - 14469. [Abstract] [Full Text] [PDF]
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K.-H. Lee, E. Wang, M.-B. Nielsen, J. Wunderlich, S. Migueles, M. Connors, S. M. Steinberg, S. A. Rosenberg, and F. M. Marincola Increased Vaccine-Specific T Cell Frequency After Peptide-Based Vaccination Correlates with Increased Susceptibility to In Vitro Stimulation But Does Not Lead to Tumor Regression J. Immunol., December 1, 1999; 163(11): 6292 - 6300. [Abstract] [Full Text] [PDF]
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A. E. Lukacher, J. M. Moser, A. Hadley, and J. D. Altman Visualization of Polyoma Virus-Specific CD8+ T Cells In Vivo During Infection and Tumor Rejection J. Immunol., September 15, 1999; 163(6): 3369 - 3378. [Abstract] [Full Text] [PDF]
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