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*
Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215; and
Beckman Coulter, Miami, FL 33116
The CTL response was characterized during primary SIV/macaque (SIVmac) infection of rhesus monkeys to assess its role in containing early viral replication using both an epitope-specific functional and an MHC class I/peptide tetramer-binding assay. The rapid expansion of a single dominant viral epitope-specific CTL population to 1.3–8.3% of circulating CD8+ peripheral blood and 0.3–1.3% of lymph node CD8+ T cells was observed, peaking at day 13 following infection. A subsequent decrease in number of these cells was then demonstrated. Interestingly, the percent of tetramer-binding CD8+ T cells detected in the lymph nodes of all evaluated animals was smaller than the percent detected in PBL. These epitope-specific CD8+ T cells expressed cell surface molecules associated with memory and activation. Early clearance of SIVmac occurred coincident with the emergence of the CTL response, suggesting that CTL may be important in containing virus replication. A higher percent of annexin V-binding cells was detected in the tetramer+ CD8+ T cells (range, from 33% to 75%) than in the remaining CD8+ T cells (range, from 3.3% to 15%) at the time of maximum CTL expansion in all evaluated animals. This finding indicates that the decrease of CTL occurred as a result of the death of these cells rather than their anatomic redistribution. These studies provide strong evidence for the importance of CTL in containing AIDS virus replication.
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J. R. Currier, M. deSouza, P. Chanbancherd, W. Bernstein, D. L. Birx, and J. H. Cox Comprehensive Screening for Human Immunodeficiency Virus Type 1 Subtype-Specific CD8 Cytotoxic T Lymphocytes and Definition of Degenerate Epitopes Restricted by HLA-A0207 and -CW0304 Alleles J. Virol., April 16, 2002; 76(10): 4971 - 4986. [Abstract] [Full Text] [PDF]
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V. Appay, L. Papagno, C. A. Spina, P. Hansasuta, A. King, L. Jones, G. S. Ogg, S. Little, A. J. McMichael, D. D. Richman, et al. Dynamics of T Cell Responses in HIV Infection J. Immunol., April 1, 2002; 168(7): 3660 - 3666. [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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T. L.-Y. Chang, A. Mosoian, R. Pine, M. E. Klotman, and J. P. Moore A Soluble Factor(s) Secreted from CD8+ T Lymphocytes Inhibits Human Immunodeficiency Virus Type 1 Replication through STAT1 Activation J. Virol., January 15, 2002; 76(2): 569 - 581. [Abstract] [Full Text] [PDF]
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L. Stevceva, B. Kelsall, J. Nacsa, M. Moniuszko, Z. Hel, E. Tryniszewska, and G. Franchini Cervicovaginal Lamina Propria Lymphocytes: Phenotypic Characterization and Their Importance in Cytotoxic T-Lymphocyte Responses to Simian Immunodeficiency Virus SIVmac251 J. Virol., January 1, 2002; 76(1): 9 - 18. [Abstract] [Full Text] [PDF]
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R. Pal, D. Venzon, N. L. Letvin, S. Santra, D. C. Montefiori, N. R. Miller, E. Tryniszewska, M. G. Lewis, T. C. VanCott, V. Hirsch, et al. ALVAC-SIV-gag-pol-env-Based Vaccination and Macaque Major Histocompatibility Complex Class I (A*01) Delay Simian Immunodeficiency Virus SIVmac-Induced Immunodeficiency J. Virol., January 1, 2002; 76(1): 292 - 302. [Abstract] [Full Text] [PDF]
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P. F. McKay, J. E. Schmitz, D. H. Barouch, M. J. Kuroda, M. A. Lifton, C. E. Nickerson, D. A. Gorgone, and N. L. Letvin Vaccine Protection Against Functional CTL Abnormalities in Simian Human Immunodeficiency Virus-Infected Rhesus Monkeys J. Immunol., January 1, 2002; 168(1): 332 - 337. [Abstract] [Full Text] [PDF]
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J. E. Schmitz, R. S. Veazey, M. J. Kuroda, D. B. Levy, A. Seth, K. G. Mansfield, C. E. Nickerson, M. A. Lifton, X. Alvarez, A. A. Lackner, et al. Simian immunodeficiency virus (SIV)-specific cytotoxic T lymphocytes in gastrointestinal tissues of chronically SIV-infected rhesus monkeys Blood, December 15, 2001; 98(13): 3757 - 3761. [Abstract] [Full Text] [PDF]
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R. A. Parker, M. M. Regan, and K. A. Reimann Variability of Viral Load in Plasma of Rhesus Monkeys Inoculated with Simian Immunodeficiency Virus or Simian-Human Immunodeficiency Virus: Implications for Using Nonhuman Primate AIDS Models To Test Vaccines and Therapeutics J. Virol., November 15, 2001; 75(22): 11234 - 11238. [Abstract] [Full Text] [PDF]
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S. Robinson, W. A. Charini, M. H. Newberg, M. J. Kuroda, C. I. Lord, and N. L. Letvin A Commonly Recognized Simian Immunodeficiency Virus Nef Epitope Presented to Cytotoxic T Lymphocytes of Indian-Origin Rhesus Monkeys by the Prevalent Major Histocompatibility Complex Class I Allele Mamu-A*02 J. Virol., November 1, 2001; 75(21): 10179 - 10186. [Abstract] [Full Text] [PDF]
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R. S. Veazey, M.-C. Gauduin, K. G. Mansfield, I. C. Tham, J. D. Altman, J. D. Lifson, A. A. Lackner, and R. P. Johnson Emergence and Kinetics of Simian Immunodeficiency Virus-Specific CD8+ T Cells in the Intestines of Macaques during Primary Infection J. Virol., November 1, 2001; 75(21): 10515 - 10519. [Abstract] [Full Text] [PDF]
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J. Munch, N. Stolte, D. Fuchs, C. Stahl-Hennig, and F. Kirchhoff Efficient Class I Major Histocompatibility Complex Down-Regulation by Simian Immunodeficiency Virus Nef Is Associated with a Strong Selective Advantage in Infected Rhesus Macaques J. Virol., November 1, 2001; 75(21): 10532 - 10536. [Abstract] [Full Text] [PDF]
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W. A. Charini, M. J. Kuroda, J. E. Schmitz, K. R. Beaudry, W. Lin, M. A. Lifton, G. R. Krivulka, A. Necker, and N. L. Letvin Clonally Diverse CTL Response to a Dominant Viral Epitope Recognizes Potential Epitope Variants J. Immunol., November 1, 2001; 167(9): 4996 - 5003. [Abstract] [Full Text] [PDF]
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M. C. G. Marcondes, E. M. E. Burudi, S. Huitron-Resendiz, M. Sanchez-Alavez, D. Watry, M. Zandonatti, S. J. Henriksen, and H. S. Fox Highly Activated CD8+ T Cells in the Brain Correlate with Early Central Nervous System Dysfunction in Simian Immunodeficiency Virus Infection J. Immunol., November 1, 2001; 167(9): 5429 - 5438. [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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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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A. Hosmalin, A. Samri, M.-J. Dumaurier, Y. Dudoit, E. Oksenhendler, M. Karmochkine, B. Autran, S. Wain-Hobson, and R. Cheynier HIV-specific effector cytotoxic T lymphocytes and HIV-producing cells colocalize in white pulps and germinal centers from infected patients Blood, May 1, 2001; 97(9): 2695 - 2701. [Abstract] [Full Text] [PDF]
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 N. L. Letvin, B. R. Bloom, and S. L. Hoffman Prospects for Vaccines to Protect Against AIDS, Tuberculosis, and Malaria JAMA, February 7, 2001; 285(5): 606 - 611. [Abstract] [Full Text] [PDF]
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T.-M. Fu, D. C. Freed, W. L. Trigona, L. Guan, L. Zhu, R. Long, N. V. Persaud, K. Manson, S. Dubey, and J. W. Shiver Evaluation of Cytotoxic T-Lymphocyte Responses in Human and Nonhuman Primate Subjects Infected with Human Immunodeficiency Virus Type 1 or Simian/Human Immunodeficiency Virus J. Virol., January 1, 2001; 75(1): 73 - 82. [Abstract] [Full Text]
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S. Reichstetter, R. A. Ettinger, A. W. Liu, J. A. Gebe, G. T. Nepom, and W. W. Kwok Distinct T Cell Interactions with HLA Class II Tetramers Characterize a Spectrum of TCR Affinities in the Human Antigen-Specific T Cell Response J. Immunol., December 15, 2000; 165(12): 6994 - 6998. [Abstract] [Full Text] [PDF]
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S. Gummuluru, C. M. Kinsey, and M. Emerman An In Vitro Rapid-Turnover Assay for Human Immunodeficiency Virus Type 1 Replication Selects for Cell-to-Cell Spread of Virus J. Virol., December 1, 2000; 74(23): 10882 - 10891. [Abstract] [Full Text]
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A. Granelli-Piperno, L. Zhong, P. Haslett, J. Jacobson, and R. M. Steinman Dendritic Cells, Infected with Vesicular Stomatitis Virus-Pseudotyped HIV-1, Present Viral Antigens to CD4+ and CD8+ T Cells from HIV-1-Infected Individuals J. Immunol., December 1, 2000; 165(11): 6620 - 6626. [Abstract] [Full Text] [PDF]
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A. J. Iafrate, S. Carl, S. Bronson, C. Stahl-Hennig, T. Swigut, J. Skowronski, and F. Kirchhoff Disrupting Surfaces of Nef Required for Downregulation of CD4 and for Enhancement of Virion Infectivity Attenuates Simian Immunodeficiency Virus Replication In Vivo J. Virol., November 1, 2000; 74(21): 9836 - 9844. [Abstract] [Full Text]
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T. C. McGuire, S. R. Leib, S. M. Lonning, W. Zhang, K. M. Byrne, and R. H. Mealey Equine infectious anaemia virus proteins with epitopes most frequently recognized by cytotoxic T lymphocytes from infected horses J. Gen. Virol., November 1, 2000; 81(11): 2735 - 2739. [Abstract] [Full Text]
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S. Goldstein, C. R. Brown, H. Dehghani, J. D. Lifson, and V. M. Hirsch Intrinsic Susceptibility of Rhesus Macaque Peripheral CD4+ T Cells to Simian Immunodeficiency Virus In Vitro Is Predictive of In Vivo Viral Replication J. Virol., October 15, 2000; 74(20): 9388 - 9395. [Abstract] [Full Text]
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A. Kaur, C. L. Hale, S. Ramanujan, R. K. Jain, and R. P. Johnson Differential Dynamics of CD4+ and CD8+ T-Lymphocyte Proliferation and Activation in Acute Simian Immunodeficiency Virus Infection J. Virol., September 15, 2000; 74(18): 8413 - 8424. [Abstract] [Full Text]
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M. J. Kuroda, J. E. Schmitz, C. Lekutis, C. E. Nickerson, M. A. Lifton, G. Franchini, J. M. Harouse, C. Cheng-Mayer, and N. L. Letvin Human Immunodeficiency Virus Type 1 Envelope Epitope-Specific CD4+ T Lymphocytes in Simian/Human Immunodeficiency Virus-Infected and Vaccinated Rhesus Monkeys Detected Using a Peptide-Major Histocompatibility Complex Class II Tetramer J. Virol., September 15, 2000; 74(18): 8751 - 8756. [Abstract] [Full Text]
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M. A. Egan, W. A. Charini, M. J. Kuroda, J. E. Schmitz, P. Racz, K. Tenner-Racz, K. Manson, M. Wyand, M. A. Lifton, C. E. Nickerson, et al. Simian Immunodeficiency Virus (SIV) gag DNA-Vaccinated Rhesus Monkeys Develop Secondary Cytotoxic T-Lymphocyte Responses and Control Viral Replication after Pathogenic SIV Infection J. Virol., August 15, 2000; 74(16): 7485 - 7495. [Abstract] [Full Text]
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M. J. Kuroda, J. E. Schmitz, A. Seth, R. S. Veazey, C. E. Nickerson, M. A. Lifton, P. J. Dailey, M. A. Forman, P. Racz, K. Tenner-Racz, et al. Simian immunodeficiency virus-specific cytotoxic T lymphocytes and cell-associated viral RNA levels in distinct lymphoid compartments of SIVmac-infected rhesus monkeys Blood, August 15, 2000; 96(4): 1474 - 1479. [Abstract] [Full Text] [PDF]
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J. E. Schmitz, M. J. Kuroda, R. S. Veazey, A. Seth, W. M. Taylor, C. E. Nickerson, M. A. Lifton, P. J. Dailey, M. A. Forman, P. Racz, et al. Simian Immunodeficiency Virus (SIV)-Specific CTL Are Present in Large Numbers in Livers of SIV-Infected Rhesus Monkeys J. Immunol., June 1, 2000; 164(11): 6015 - 6019. [Abstract] [Full Text] [PDF]
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T. M. Allen, T. U. Vogel, D. H. Fuller, B. R. Mothe, S. Steffen, J. E. Boyson, T. Shipley, J. Fuller, T. Hanke, A. Sette, et al. Induction of AIDS Virus-Specific CTL Activity in Fresh, Unstimulated Peripheral Blood Lymphocytes from Rhesus Macaques Vaccinated with a DNA Prime/Modified Vaccinia Virus Ankara Boost Regimen J. Immunol., May 1, 2000; 164(9): 4968 - 4978. [Abstract] [Full Text] [PDF]
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S. Aung and B. S. Graham IL-4 Diminishes Perforin-Mediated and Increases Fas Ligand-Mediated Cytotoxicity In Vivo J. Immunol., April 1, 2000; 164(7): 3487 - 3493. [Abstract] [Full Text] [PDF]
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A. Seth, I. Ourmanov, J. E. Schmitz, M. J. Kuroda, M. A. Lifton, C. E. Nickerson, L. Wyatt, M. Carroll, B. Moss, D. Venzon, et al. Immunization with a Modified Vaccinia Virus Expressing Simian Immunodeficiency Virus (SIV) Gag-Pol Primes for an Anamnestic Gag-Specific Cytotoxic T-Lymphocyte Response and Is Associated with Reduction of Viremia after SIV Challenge J. Virol., March 15, 2000; 74(6): 2502 - 2509. [Abstract] [Full Text]
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I. Ourmanov, C. R. Brown, B. Moss, M. Carroll, L. Wyatt, L. Pletneva, S. Goldstein, D. Venzon, and V. M. Hirsch Comparative Efficacy of Recombinant Modified Vaccinia Virus Ankara Expressing Simian Immunodeficiency Virus (SIV) Gag-Pol and/or Env in Macaques Challenged with Pathogenic SIV J. Virol., March 15, 2000; 74(6): 2740 - 2751. [Abstract] [Full Text]
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L. D. Giavedoni, M. C. Velasquillo, L. M. Parodi, G. B. Hubbard, and V. L. Hodara Cytokine Expression, Natural Killer Cell Activation, and Phenotypic Changes in Lymphoid Cells from Rhesus Macaques during Acute Infection with Pathogenic Simian Immunodeficiency Virus J. Virol., February 15, 2000; 74(4): 1648 - 1657. [Abstract] [Full Text]
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A. Kaur, J. Yang, D. Hempel, L. Gritz, G. P. Mazzara, H. McClure, and R. P. Johnson Identification of Multiple Simian Immunodeficiency Virus (SIV)-Specific CTL Epitopes in Sooty Mangabeys with Natural and Experimentally Acquired SIV Infection J. Immunol., January 15, 2000; 164(2): 934 - 943. [Abstract] [Full Text] [PDF]
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M. A. Egan, M. J. Kuroda, G. Voss, J. E. Schmitz, W. A. Charini, C. I. Lord, M. A. Forman, and N. L. Letvin Use of Major Histocompatibility Complex Class I/Peptide/beta 2M Tetramers To Quantitate CD8+ Cytotoxic T Lymphocytes Specific for Dominant and Nondominant Viral Epitopes in Simian-Human Immunodeficiency Virus-Infected Rhesus Monkeys J. Virol., July 1, 1999; 73(7): 5466 - 5472. [Abstract] [Full Text]
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F. Cocchi, A. L. DeVico, R. Yarchoan, R. Redfield, F. Cleghorn, W. A. Blattner, A. Garzino-Demo, S. Colombini-Hatch, D. Margolis, and R. C. Gallo Higher macrophage inflammatory protein (MIP)-1alpha and MIP-1beta levels from CD8+ T cells are associated with asymptomatic HIV-1 infection PNAS, December 5, 2000; 97(25): 13812 - 13817. [Abstract] [Full Text] [PDF]
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