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

Nichole R. Klatt, Francois Villinger, Pavel Bostik, Shari N. Gordon, Lara Pereira, Jessica C. Engram, Ann Mayne, Richard M. Dunham, Benton Lawson, Sarah J. Ratcliffe, Donald L. Sodora, James Else, Keith Reimann, Silvija I. Staprans, Ashley T. Haase, Jacob Estes, Guido Silvestri, Aftab A. Ansari

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)2039-2049
Number of pages11
JournalJournal of Clinical Investigation
Volume118
Issue number6
DOIs
StatePublished - Jun 2 2008
Externally publishedYes

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Cercocebus atys
Viremia
T-Lymphocytes
Virus Replication
Viral Load
Acquired Immunodeficiency Syndrome
Monocytes
Mucous Membrane

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Klatt, N. R., Villinger, F., Bostik, P., Gordon, S. N., Pereira, L., Engram, J. C., ... Ansari, A. A. (2008). Availability of activated CD4+ T cells dictates the level of viremia in naturally SIV-infected sooty mangabeys. Journal of Clinical Investigation, 118(6), 2039-2049. https://doi.org/10.1172/JCI33814

Availability of activated CD4+ T cells dictates the level of viremia in naturally SIV-infected sooty mangabeys. / Klatt, Nichole R.; Villinger, Francois; Bostik, Pavel; Gordon, Shari N.; Pereira, Lara; Engram, Jessica C.; Mayne, Ann; Dunham, Richard M.; Lawson, Benton; Ratcliffe, Sarah J.; Sodora, Donald L.; Else, James; Reimann, Keith; Staprans, Silvija I.; Haase, Ashley T.; Estes, Jacob; Silvestri, Guido; Ansari, Aftab A.

In: Journal of Clinical Investigation, Vol. 118, No. 6, 02.06.2008, p. 2039-2049.

Research output: Contribution to journalArticle

Klatt, NR, Villinger, F, Bostik, P, Gordon, SN, Pereira, L, Engram, JC, Mayne, A, Dunham, RM, Lawson, B, Ratcliffe, SJ, Sodora, DL, Else, J, Reimann, K, Staprans, SI, Haase, AT, Estes, J, Silvestri, G & Ansari, AA 2008, 'Availability of activated CD4+ T cells dictates the level of viremia in naturally SIV-infected sooty mangabeys', Journal of Clinical Investigation, vol. 118, no. 6, pp. 2039-2049. https://doi.org/10.1172/JCI33814
Klatt, Nichole R. ; Villinger, Francois ; Bostik, Pavel ; Gordon, Shari N. ; Pereira, Lara ; Engram, Jessica C. ; Mayne, Ann ; Dunham, Richard M. ; Lawson, Benton ; Ratcliffe, Sarah J. ; Sodora, Donald L. ; Else, James ; Reimann, Keith ; Staprans, Silvija I. ; Haase, Ashley T. ; Estes, Jacob ; Silvestri, Guido ; Ansari, Aftab A. / Availability of activated CD4+ T cells dictates the level of viremia in naturally SIV-infected sooty mangabeys. In: Journal of Clinical Investigation. 2008 ; Vol. 118, No. 6. pp. 2039-2049.
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AU - Gordon, Shari N.

AU - Pereira, Lara

AU - Engram, Jessica C.

AU - Mayne, Ann

AU - Dunham, Richard M.

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AU - Else, James

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