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Availability of activated CD4(+) T cells dictates the level of viremia in naturally SIV-infected sooty mangabeys

  1. Author:
    Klatt, N. R.
    Villinger, F.
    Bostik, P.
    Gordon, S. N.
    Pereira, L.
    Engram, J. C.
    Mayne, A.
    Dunham, R. M.
    Lawson, B.
    Ratcliffe, S. J.
    Sodora, D. L.
    Else, J.
    Reimann, K.
    Staprans, S. I.
    Haase, A. T.
    Estes, J. D.
    Silvestri, G.
    Ansari, A. A.

  2. Author Address

    Klatt, Nichole R.; Gordon, Shari N.; Engram, Jessica C.; Dunham, Richard M.; Silvestri, Guido] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Villinger, Francois, Bostik, Pavel, Pereira, Lara, Mayne, Ann, Ansari, Aftab A.] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Klatt, Nichole R.; Villinger, Francois, Gordon, Shari N.; Dunham, Richard M.; Lawson, Benton, Else, James, Silvestri, Guido, Ansari, Aftab A.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Ratcliffe, Sarah J.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Sodora, Donald L.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Sodora, Donald L.] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA. [Reimann, Keith] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Staprans, Silvija I.] Merck Vaccines, West Point, PA USA. [Haase, Ashley T.] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA. [Estes, Jacob D.] NCI, Sci Applicat Int Corp, AIDS & Canc Virus Program, Frederick, MD 21701 USA.
    1. Year: 2008
  2. Journal: Journal of Clinical Investigation
    1. 118
    2. 6
    3. Pages: 2039-2049
  4. Type of Article: Article
  1. Abstract:

    Naturally SIV-infected sooty mangabeys (SMs) remain asymptomatic despite high virus replication. Elucidating the mechanisms underlying AIDS resistance of SIV-infected SMs may provide crucial information to better understand AIDS pathogenesis. In this study, we assessed the determinants of set-point viremia in naturally SIV-infected SMs, i.e., immune control of SIV replication versus target cell limitation. We depleted CD4(+) T cells in 6 naturally SIV-infected SMs by treating with humanized anti-CD4 mAb (Cdr-OKT4A-huIgG1). CD4(+) T cells were depleted almost completely in blood and BM and at variable levels in mucosal tissues and LNs. No marked depletion of CD14(+) monocytes was observed. Importantly, CD4(+) T cell depletion was associated with a rapid, significant decline in viral load, which returned to baseline level at day 30-45, coincident with an increased fraction of proliferating and activated CD4(+) T cells. Throughout the study, virus replication correlated with the level of proliferating CD4(+) T cells. CD4(+) T cell depletion did not induce any changes in the fraction of Tregs or the level of SIV-specific CD8(+) T cells. Our results suggest that the availability of activated CD4(+) T cells, rather than immune control of SIV replication, is the main determinant of set-point viral load during natural SIV infection of SMs.

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External Sources

  1. PMID: 18497876

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