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The Journal of Immunology, 1999, 162: 5127-5133.
Copyright © 1999 by The American Association of Immunologists

Emergence of CTL Coincides with Clearance of Virus During Primary Simian Immunodeficiency Virus Infection in Rhesus Monkeys1

Marcelo J. Kuroda2,*, Jörn E. Schmitz*, William A. Charini*, Christine E. Nickerson*, Michelle A. Lifton*, Carol I. Lord*, Meryl A. Forman{dagger} and Norman L. Letvin*

* Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215; and {dagger} 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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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.
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BloodHome page
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.
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J. Virol.Home page
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.
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J. Virol.Home page
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.
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J. Virol.Home page
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.
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J. Virol.Home page
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.
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