4.8 Article

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

期刊

JOURNAL OF CLINICAL INVESTIGATION
卷 118, 期 6, 页码 2039-2049

出版社

AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI33814

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资金

  1. NCRR NIH HHS [R24 RR016988, R24RR16988, RR-00165, R24 RR016001, P51 RR000165, RR016001] Funding Source: Medline
  2. NHLBI NIH HHS [R01-HL-75766, R01 HL075766] Funding Source: Medline
  3. NIAID NIH HHS [R01 AI066998, R01-AI27057, R01 AI040101, R21-AI060451, AI040101, R01-AI66998, R01 AI027057, R21 AI060451] Funding Source: Medline

向作者/读者索取更多资源

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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