Dramatic Rise in Plasma Viremia after CD8+ T Cell Depletion in Simian Immunodeficiency Virus-infected Macaques

doi:10.1084/jem.189.6.991

A correction to this article has been published: J. Exp. Med. 189 (12) 1999-2000

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J. Exp. Med., Volume 189, Number 6, March 15, 1999 991-998

Dramatic Rise in Plasma Viremia after CD8⁺ T Cell Depletion in Simian Immunodeficiency Virus-infected Macaques

By Xia Jin,^* Daniel E. Bauer,^* Sarah E. Tuttleton,^* Sharon Lewin,^* Agegnehu Gettie,^* James Blanchard, Craig E. Irwin,^* Jeffrey T. Safrit,^§ John Mittler, Leor Weinberger, Leondios G. Kostrikis,^* Linqi Zhang,^* Alan S. Perelson, and David D. Ho^*

From ^* The Aaron Diamond AIDS Research Center, The Rockefeller University, New York 10016; Tulane Regional Primate Research Center, Covington, Louisiana 70433; the ^§ Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30329; and Los Alamos National Laboratory, Los Alamos, New Mexico 87545

To determine the role of CD8⁺ T cells in controlling simian immunodeficiency virus (SIV) replication in vivo, we examined theeffect of depleting this cell population using an anti-CD8 monoclonalantibody, OKT8F. There was on average a 99.9% reduction of CD8cells in peripheral blood in six infected Macaca mulatta treatedwith OKT8F. The apparent CD8 depletion started 1 h after antibodyadministration, and low CD8 levels were maintained until day 8.An increase in plasma viremia of one to three orders of magnitudewas observed in five of the six macaques. The injection of a controlantibody to an infected macaque did not induce a sustained viralload increase, nor did it significantly reduce the number of CD8⁺ T cells. These results demonstrate that CD8 cells play a crucialrole in suppressing SIV replication invivo.

Key words: simian immunodeficiency virus; macaque; OKT8; viremia; cytotoxic T lymphocyte

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Horton, H., Frank, I., Baydo, R., Jalbert, E., Penn, J., Wilson, S., McNevin, J. P., McSweyn, M. D., Lee, D., Huang, Y., De Rosa, S. C., McElrath, M. J. (2006). Preservation of T Cell Proliferation Restricted by Protective HLA Alleles Is Critical for Immune Control of HIV-1 Infection. J. Immunol. 177: 7406-7415 [Abstract] [Full Text]
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Kornbluth, R. S., Stone, G. W. (2006). Immunostimulatory combinations: designing the next generation of vaccine adjuvants. J. Leukoc. Biol. 80: 1084-1102 [Abstract] [Full Text]
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Weaver, E. A., Lu, Z., Camacho, Z. T., Moukdar, F., Liao, H.-X., Ma, B.-J., Muldoon, M., Theiler, J., Nabel, G. J., Letvin, N. L., Korber, B. T., Hahn, B. H., Haynes, B. F., Gao, F. (2006). Cross-Subtype T-Cell Immune Responses Induced by a Human Immunodeficiency Virus Type 1 Group M Consensus Env Immunogen. J. Virol. 80: 6745-6756 [Abstract] [Full Text]
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Betts, M. R., Nason, M. C., West, S. M., De Rosa, S. C., Migueles, S. A., Abraham, J., Lederman, M. M., Benito, J. M., Goepfert, P. A., Connors, M., Roederer, M., Koup, R. A. (2006). HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood 107: 4781-4789 [Abstract] [Full Text]
Mattapallil, J. J., Douek, D. C., Buckler-White, A., Montefiori, D., Letvin, N. L., Nabel, G. J., Roederer, M. (2006). Vaccination preserves CD4 memory T cells during acute simian immunodeficiency virus challenge. JEM 203: 1533-1541 [Abstract] [Full Text]
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Turnbull, E. L., Lopes, A. R., Jones, N. A., Cornforth, D., Newton, P., Aldam, D., Pellegrino, P., Turner, J., Williams, I., Wilson, C. M., Goepfert, P. A., Maini, M. K., Borrow, P. (2006). HIV-1 Epitope-Specific CD8+ T Cell Responses Strongly Associated with Delayed Disease Progression Cross-Recognize Epitope Variants Efficiently. J. Immunol. 176: 6130-6146 [Abstract] [Full Text]
Goonetilleke, N., Moore, S., Dally, L., Winstone, N., Cebere, I., Mahmoud, A., Pinheiro, S., Gillespie, G., Brown, D., Loach, V., Roberts, J., Guimaraes-Walker, A., Hayes, P., Loughran, K., Smith, C., De Bont, J., Verlinde, C., Vooijs, D., Schmidt, C., Boaz, M., Gilmour, J., Fast, P., Dorrell, L., Hanke, T., McMichael, A. J. (2006). Induction of Multifunctional Human Immunodeficiency Virus Type 1 (HIV-1)-Specific T Cells Capable of Proliferation in Healthy Subjects by Using a Prime-Boost Regimen of DNA- and Modified Vaccinia Virus Ankara-Vectored Vaccines Expressing HIV-1 Gag Coupled to CD8+ T-Cell Epitopes.. J. Virol. 80: 4717-4728 [Abstract] [Full Text]
Liu, J., Chen, I., Du, Q., Chua, H., Kwang, J. (2006). The ORF3 Protein of Porcine Circovirus Type 2 Is Involved in Viral Pathogenesis In Vivo.. J. Virol. 80: 5065-5073 [Abstract] [Full Text]
Belyakov, I. M., Kuznetsov, V. A., Kelsall, B., Klinman, D., Moniuszko, M., Lemon, M., Markham, P. D., Pal, R., Clements, J. D., Lewis, M. G., Strober, W., Franchini, G., Berzofsky, J. A. (2006). Impact of vaccine-induced mucosal high-avidity CD8+CTLs in delay of AIDS viral dissemination from mucosa. Blood 107: 3258-3264 [Abstract] [Full Text]
Pal, R., Venzon, D., Santra, S., Kalyanaraman, V. S., Montefiori, D. C., Hocker, L., Hudacik, L., Rose, N., Nacsa, J., Edghill-Smith, Y., Moniuszko, M., Hel, Z., Belyakov, I. M., Berzofsky, J. A., Parks, R. W., Markham, P. D., Letvin, N. L., Tartaglia, J., Franchini, G. (2006). Systemic Immunization with an ALVAC-HIV-1/Protein Boost Vaccine Strategy Protects Rhesus Macaques from CD4+ T-Cell Loss and Reduces both Systemic and Mucosal Simian-Human Immunodeficiency Virus SHIVKU2 RNA Levels.. J. Virol. 80: 3732-3742 [Abstract] [Full Text]
Wang, Z., Metcalf, B., Ribeiro, R. M., McClure, H., Kaur, A. (2006). Th-1-Type Cytotoxic CD8+ T-Lymphocyte Responses to Simian Immunodeficiency Virus (SIV) Are a Consistent Feature of Natural SIV Infection in Sooty Mangabeys. J. Virol. 80: 2771-2783 [Abstract] [Full Text]
Quigley, M. F., Abel, K., Zuber, B., Miller, C. J., Sandberg, J. K., Shacklett, B. L. (2006). Perforin Expression in the Gastrointestinal Mucosa Is Limited to Acute Simian Immunodeficiency Virus Infection. J. Virol. 80: 3083-3087 [Abstract] [Full Text]
Lauren, A., Thorstensson, R., Fenyo, E. M. (2006). Comparative studies on mucosal and intravenous transmission of simian immunodeficiency virus (SIVsm): the kinetics of evolution to neutralization resistance are related to progression rate of disease.. J. Gen. Virol. 87: 595-606 [Abstract] [Full Text]
Kawada, M., Igarashi, H., Takeda, A., Tsukamoto, T., Yamamoto, H., Dohki, S., Takiguchi, M., Matano, T. (2006). Involvement of Multiple Epitope-Specific Cytotoxic T-Lymphocyte Responses in Vaccine-Based Control of Simian Immunodeficiency Virus Replication in Rhesus Macaques. J. Virol. 80: 1949-1958 [Abstract] [Full Text]
Yu, Q., Yue, F. Y., Gu, X. X., Schwartz, H., Kovacs, C. M., Ostrowski, M. A. (2006). OX40 Ligation of CD4+ T Cells Enhances Virus-Specific CD8+ T Cell Memory Responses Independently of IL-2 and CD4+ T Regulatory Cell Inhibition. J. Immunol. 176: 2486-2495 [Abstract] [Full Text]