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Science 5 February 1999:
Vol. 283. no. 5403, pp. 857 - 860
DOI: 10.1126/science.283.5403.857
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Reports

Control of Viremia in Simian Immunodeficiency Virus Infection by CD8+ Lymphocytes

Jörn E. Schmitz, 1* Marcelo J. Kuroda, 1 Sampa Santra, 1 Vito G. Sasseville, 2dagger Meredith A. Simon, 2 Michelle A. Lifton, 1 Paul Racz, 3 Klara Tenner-Racz, 3 Margaret Dalesandro, 4ddagger Bernhard J. Scallon, 4 John Ghrayeb, 4 Meryl A. Forman, 5 David C. Montefiori, 6 E. Peter Rieber, 7 Norman L. Letvin, 1 Keith A. Reimann 1*

Clinical evidence suggests that cellular immunity is involved in controlling human immunodeficiency virus-1 (HIV-1) replication. An animal model of acquired immune deficiency syndrome (AIDS), the simian immunodeficiency virus (SIV)-infected rhesus monkey, was used to show that virus replication is not controlled in monkeys depleted of CD8+ lymphocytes during primary SIV infection. Eliminating CD8+ lymphocytes from monkeys during chronic SIV infection resulted in a rapid and marked increase in viremia that was again suppressed coincident with the reappearance of SIV-specific CD8+ T cells. These results confirm the importance of cell-mediated immunity in controlling HIV-1 infection and support the exploration of vaccination approaches for preventing infection that will elicit these immune responses.

1 Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
2 New England Regional Primate Research Center, Harvard Medical School, Southborough, MA 01772, USA.
3 Bernhard-Nocht-Institute for Tropical Medicine, 20359 Hamburg, Germany.
4 Centocor, Malvern, PA 19355, USA.
5 Beckman Coulter, Miami, FL 33196, USA.
6 Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
7 Institute of Immunology, Technical University of Dresden, 01101 Dresden, Germany.
*   To whom correspondence should be addressed. E-mail: jschmitz{at}caregroup.harvard.edu; kreimann{at}caregroup.harvard.edu

dagger    Present address: Bristol-Myers Squibb, PRI, Department of Experimental Pathology, Princeton, NJ 08540, USA.

ddagger    Present address: Cambridge Pharma Consultancy, North America Office, New York, NY 10022.

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   Abstract »    Full Text »    PDF »
Immune-response profiles induced by human immunodeficiency virus type 1 vaccine DNA, protein or mixed-modality immunization: increased protection from pathogenic simian human immunodeficiency virus viraemia with protein/DNA combination.
G. Koopman, D. Mortier, S. Hofman, N. Mathy, M. Koutsoukos, P. Ertl, P. Overend, C. van Wely, L. L. Thomsen, B. Wahren, et al. (2008)
J. Gen. Virol. 89, 540-5533
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Therapeutic Immunization with Human Immunodeficiency Virus Type 1 (HIV-1) Peptide-Loaded Dendritic Cells Is Safe and Induces Immunogenicity in HIV-1-Infected Individuals.
N. C. Connolly, T. L. Whiteside, C. Wilson, V. Kondragunta, C. R. Rinaldo, and S. A. Riddler (2008)
Clin. Vaccine Immunol. 15, 284-292
   Abstract »    Full Text »    PDF »
The failed HIV Merck vaccine study: a step back or a launching point for future vaccine development?.
R.-P. Sekaly (2008)
J. Exp. Med. 205, 7-12
   Abstract »    Full Text »    PDF »
An HIV-1 clade C DNA prime, NYVAC boost vaccine regimen induces reliable, polyfunctional, and long-lasting T cell responses.
A. Harari, P.-A. Bart, W. Stohr, G. Tapia, M. Garcia, E. Medjitna-Rais, S. Burnet, C. Cellerai, O. Erlwein, T. Barber, et al. (2008)
J. Exp. Med. 205, 63-77
   Abstract »    Full Text »    PDF »
CTL-Mediated Selective Pressure Influences Dynamic Evolution and Pathogenic Functions of HIV-1 Nef.
T. Ueno, C. Motozono, S. Dohki, P. Mwimanzi, S. Rauch, O. T. Fackler, S. Oka, and M. Takiguchi (2008)
J. Immunol. 180, 1107-1116
   Abstract »    Full Text »    PDF »
Recognition of Escape Variants in ELISPOT Does Not Always Predict CD8+ T-Cell Recognition of Simian Immunodeficiency Virus-Infected Cells Expressing the Same Variant Sequences.
L. E. Valentine, S. M. Piaskowski, E. G. Rakasz, N. L. Henry, N. A. Wilson, and D. I. Watkins (2008)
J. Virol. 82, 575-581
   Abstract »    Full Text »    PDF »
HIV-1 Tat Suppresses gp120-Specific T Cell Response in IL-10-Dependent Manner.
S. Gupta, R. Boppana, G. C. Mishra, B. Saha, and D. Mitra (2008)
J. Immunol. 180, 79-88
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IL-15 Treatment during Acute Simian Immunodeficiency Virus (SIV) Infection Increases Viral Set Point and Accelerates Disease Progression despite the Induction of Stronger SIV-Specific CD8+ T Cell Responses.
Y. M. Mueller, D. H. Do, S. R. Altork, C. M. Artlett, E. J. Gracely, C. D. Katsetos, A. Legido, F. Villinger, J. D. Altman, C. R. Brown, et al. (2008)
J. Immunol. 180, 350-360
   Abstract »    Full Text »    PDF »
A High Viral Burden Predicts the Loss of CD8 T-Cell Responses Specific for Subdominant Gag Epitopes during Chronic Human Immunodeficiency Virus Infection.
C. Geldmacher, C. Gray, M. Nason, J. R. Currier, A. Haule, L. Njovu, S. Geis, O. Hoffmann, L. Maboko, A. Meyerhans, et al. (2007)
J. Virol. 81, 13809-13815
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Dynamics of T-Cell Responses and Memory T Cells during Primary Simian Immunodeficiency Virus Infection in Cynomolgus Macaques.
I. Karlsson, B. Malleret, P. Brochard, B. Delache, J. Calvo, R. Le Grand, and B. Vaslin (2007)
J. Virol. 81, 13456-13468
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4-1BBL Induces TNF Receptor-Associated Factor 1-Dependent Bim Modulation in Human T Cells and Is a Critical Component in the Costimulation-Dependent Rescue of Functionally Impaired HIV-Specific CD8 T Cells.
C. Wang, T. Wen, J.-P. Routy, N. F. Bernard, R. P. Sekaly, and T. H. Watts (2007)
J. Immunol. 179, 8252-8263
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Utility of Human Immunodeficiency Virus Type 1 Envelope as a T-Cell Immunogen.
V. Peut and S. J. Kent (2007)
J. Virol. 81, 13125-13134
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Differential natural killer cell mediated inhibition of HIV-1 replication based on distinct KIR/HLA subtypes.
G. Alter, M. P. Martin, N. Teigen, W. H. Carr, T. J. Suscovich, A. Schneidewind, H. Streeck, M. Waring, A. Meier, C. Brander, et al. (2007)
J. Exp. Med. 204, 3027-3036
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Escape from the Dominant HLA-B27-Restricted Cytotoxic T-Lymphocyte Response in Gag Is Associated with a Dramatic Reduction in Human Immunodeficiency Virus Type 1 Replication.
A. Schneidewind, M. A. Brockman, R. Yang, R. I. Adam, B. Li, S. Le Gall, C. R. Rinaldo, S. L. Craggs, R. L. Allgaier, K. A. Power, et al. (2007)
J. Virol. 81, 12382-12393
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Induction of CD8+ Cells Able To Suppress CCR5-Tropic Simian Immunodeficiency Virus SIVmac239 Replication by Controlled Infection of CXCR4-Tropic Simian-Human Immunodeficiency Virus in Vaccinated Rhesus Macaques.
T. Tsukamoto, M. Yuasa, H. Yamamoto, M. Kawada, A. Takeda, H. Igarashi, and T. Matano (2007)
J. Virol. 81, 11640-11649
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AIDS virus specific CD8+ T lymphocytes against an immunodominant cryptic epitope select for viral escape.
N. J. Maness, L. E. Valentine, G. E. May, J. Reed, S. M. Piaskowski, T. Soma, J. Furlott, E. G. Rakasz, T. C. Friedrich, D. A. Price, et al. (2007)
J. Exp. Med. 204, 2505-2512
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Early Establishment and Antigen Dependence of Simian Immunodeficiency Virus-Specific CD8+ T-Cell Defects.
Y. M. Mueller, C. Petrovas, D. H. Do, S. R. Altork, T. Fischer-Smith, J. Rappaport, J. D. Altman, M. G. Lewis, and P. D. Katsikis (2007)
J. Virol. 81, 10861-10868
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Human Immunodeficiency Virus Type 1 Derivative with 7% Simian Immunodeficiency Virus Genetic Content Is Able To Establish Infections in Pig-Tailed Macaques.
T. Igarashi, R. Iyengar, R. A. Byrum, A. Buckler-White, R. L. Dewar, C. E. Buckler, H. C. Lane, K. Kamada, A. Adachi, and M. A. Martin (2007)
J. Virol. 81, 11549-11552
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Killing Kinetics of Simian Immunodeficiency Virus-Specific CD8+ T Cells: Implications for HIV Vaccine Strategies.
E. Rollman, M. Z. Smith, A. G. Brooks, D. F. J. Purcell, B. Zuber, I. A. Ramshaw, and S. J. Kent (2007)
J. Immunol. 179, 4571-4579
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Live Attenuated Lentivirus Infection Elicits Polyfunctional Simian Immunodeficiency Virus Gag-Specific CD8+ T Cells with Reduced Apoptotic Susceptibility in Rhesus Macaques that Control Virus Replication after Challenge with Pathogenic SIVmac239.
M. Genesca, T. Rourke, J. Li, K. Bost, B. Chohan, M. B. McChesney, and C. J. Miller (2007)
J. Immunol. 179, 4732-4740
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Induction of Potent CD8+ T-Cell Responses by Novel Biodegradable Nanoparticles Carrying Human Immunodeficiency Virus Type 1 gp120.
X. Wang, T. Uto, T. Akagi, M. Akashi, and M. Baba (2007)
J. Virol. 81, 10009-10016
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Adenoviral vectors persist in vivo and maintain activated CD8+ T cells: implications for their use as vaccines.
N. Tatsis, J. C. Fitzgerald, A. Reyes-Sandoval, K. C. Harris-McCoy, S. E. Hensley, D. Zhou, S.-W. Lin, A. Bian, Z. Q. Xiang, A. Iparraguirre, et al. (2007)
Blood 110, 1916-1923
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A Rapid Progressor-Specific Variant Clone of Simian Immunodeficiency Virus Replicates Efficiently In Vivo Only in the Absence of Immune Reponses.
T. Kuwata, R. Byrum, S. Whitted, R. Goeken, A. Buckler-White, R. Plishka, R. Iyengar, and V. M. Hirsch (2007)
J. Virol. 81, 8891-8904
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Viral Replication Capacity as a Correlate of HLA B57/B5801-Associated Nonprogressive HIV-1 Infection.
M. Navis, I. Schellens, D. van Baarle, J. Borghans, P. van Swieten, F. Miedema, N. Kootstra, and H. Schuitemaker (2007)
J. Immunol. 179, 3133-3143
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SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection.
C. Petrovas, D. A. Price, J. Mattapallil, D. R. Ambrozak, C. Geldmacher, V. Cecchinato, M. Vaccari, E. Tryniszewska, E. Gostick, M. Roederer, et al. (2007)
Blood 110, 928-936
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Neutralizing Antibody Responses in Acute Human Immunodeficiency Virus Type 1 Subtype C Infection.
E. S. Gray, P. L. Moore, I. A. Choge, J. M. Decker, F. Bibollet-Ruche, H. Li, N. Leseka, F. Treurnicht, K. Mlisana, G. M. Shaw, et al. (2007)
J. Virol. 81, 6187-6196
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Depletion of CD8+ Cells in Sooty Mangabey Monkeys Naturally Infected with Simian Immunodeficiency Virus Reveals Limited Role for Immune Control of Virus Replication in a Natural Host Species.
A. P. Barry, G. Silvestri, J. T. Safrit, B. Sumpter, N. Kozyr, H. M. McClure, S. I. Staprans, and M. B. Feinberg (2007)
J. Immunol. 178, 8002-8012
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Immunization with vaccinia virus induces polyfunctional and phenotypically distinctive CD8+ T cell responses.
M. L. Precopio, M. R. Betts, J. Parrino, D. A. Price, E. Gostick, D. R. Ambrozak, T. E. Asher, D. C. Douek, A. Harari, G. Pantaleo, et al. (2007)
J. Exp. Med. 204, 1405-1416
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