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Increased loss of CCR5(+) CD45RA(-) CD4(+) T cells in CD8(+) lymphocyte-depleted simian immunodeficiency virus-infected rhesus monkeys

  1. Author:
    Veazey, R. S.
    Acierno, P. M.
    McEvers, K. J.
    Baumeister, S.
    Foster, G. J.
    Rett, M. D.
    Newberg, M. H.
    Kuroda, M. J.
    Williams, K.
    Kim, E. Y.
    Wolinsky, S. M.
    Rieber, E. P.
    Piatak, M.
    Lifson, J. D.
    Montefiori, D. C.
    Brown, C. R.
    Hirsch, V.

  2. Author Address

    Acierno, Paula M.; McEvers, Kimberly J.; Baumeister, Susanne H. C.; Foster, Gabriel J.; Rett, Melisa D.; Newberg, Michael H.; Williams, Kenneth, Schmitz, Jm E.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02115 USA. [Veazey, Ronald S.; Kuroda, Marcelo J.] Tulane Univ, Sch Med, Tulane Natl Primate Res Ctr, Covington, LA 70433 USA. [Kim, Eun-Young, Wolinsky, Steven M.] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA. [Rieber, E. Peter] Tech Univ Dresden, Inst Immunol, D-01101 Dresden, Germany. [Piatak, Michael, Jr.; Lifson, Jeffrey D.] NCI, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Brown, Charles R.; Hirsch, Vanessa A.] NIAID, Mol Microbiol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA.
    1. Year: 2008
  2. Journal: Journal of Virology
    1. 82
    2. 11
    3. Pages: 5618-5630
  4. Type of Article: Article
  1. Abstract:

    Previously we have shown that CD8(+) T cells are critical for containment of simian immunodeficiency virus (SIV) viremia and that rapid and profound depletion of CD4(+) T cells occurs in the intestinal tract of acutely infected macaques. To determine the impact of SIV-specific CD8(+) T-cell responses on the magnitude of the CD4(+) T-cell depletion, we investigated the effect of CD8(+) lymphocyte depletion during primary SIV infection on CD4(+) T-cell subsets and function in peripheral blood, lymph nodes, and intestinal tissues. In peripheral blood, CD8(+) lymphocyte-depletion changed the dynamics of CD4(+) T-cell loss, resulting in a more pronounced loss 2 weeks after infection, followed by a temporal rebound approximately 2 months after infection, when absolute numbers of CD4(+) T cells were restored to baseline levels. These CD4(+) T cells showed a markedly skewed phenotype, however, as there were decreased levels of memory cells in CD8(+) lymphocyte-depleted macaques compared to controls. In intestinal tissues and lymph nodes, we observed a significantly higher loss of CCR5(+) CD45RA(-) CD4(+) T cells in CD8(+) lymphocyte-depleted macaques than in controls, suggesting that these SIV-targeted CD4(+) T cells were eliminated more efficiently in CD8(+) lymphocyte-depleted animals. Also, CD8(+) lymphocyte depletion significantly affected the ability to generate SIV Gag-specific CD4(+) T-cell responses and neutralizing antibodies. These results reemphasize that SIV-specific CD8(+) T-cell responses are absolutely critical to initiate at least partial control of SIV infection.

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External Sources

  1. PMID: 18367534

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