Availability of activated CD4+ T cells dictates the level of viremia in naturally SIV-infected sooty mangabeys
Nichole R. Klatt, … , Guido Silvestri, Aftab A. Ansari
Nichole R. Klatt, … , Guido Silvestri, Aftab A. Ansari
Published May 22, 2008
Citation Information: J Clin Invest. 2008;118(6):2039-2049. https://doi.org/10.1172/JCI33814.
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Research Article Virology

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

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.

Authors

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 D. Estes, Guido Silvestri, Aftab A. Ansari

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Figure 6

Analysis of TCR repertoire diversity via TCR V-J fragment–specific Southern hybridization.

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Analysis of TCR repertoire diversity via TCR V-J fragment–specific South...
TCR V-J PCR amplicons were generated from 3 aliquots of CD4+ T cells from each PBMC sample designated as control, 1, and 2 and hybridized with a probe generated from the control aliquot. The 1.0 signal obtained from the positive control indicates 100% homology between the probe and target; ratios from aliquots 1 and 2 indicate less homology between the probe and the amplicon and indicate the level of variability of V-J region sequences. There was no significant difference in the variability of the CD4+ T cell V-J fragment before and after CD4+ T cell depletion.