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Levels of circulating myeloid subpopulations and of heme oxygenase-1 do not predict CD4(+) T cell recovery after the initiation of antiretroviral therapy for HIV disease.

Seu L, Ortiz GM, Burt TD, Deeks SG, Martin JN, McCune JM - AIDS Res Ther (2014)

Bottom Line: We hypothesized that such variation and/or differences in the degree to which these cells expressed the immunoregulatory enzyme, heme oxygenase-1 (HO-1), would be associated with CD4(+) T cell recovery after the initiation of ART.This hypothesis was tested in a cross-sectional study of four groups of HIV-infected subjects, including those who were seronegative, untreated virologic controllers [detectable viral load (VL) of <1000 copies/mL], untreated virologic non-controllers [VL > 10,000 copies/mL], and ART-mediated virologic controllers [VL < 75 copies/mL].Among peripheral blood mononuclear cells (PBMCs), HO-1 was found to be most highly up-regulated in CD14(+) monocytes after ex vivo stimulation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA 94110, USA ; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94110, USA.

ABSTRACT
The level (or frequency) of circulating monocyte subpopulations such as classical (CD14(hi)CD16(-)) and non-classical (CD14(dim)CD16(+)) monocytes varies during the course of HIV disease progression and antiretroviral therapy (ART). We hypothesized that such variation and/or differences in the degree to which these cells expressed the immunoregulatory enzyme, heme oxygenase-1 (HO-1), would be associated with CD4(+) T cell recovery after the initiation of ART. This hypothesis was tested in a cross-sectional study of four groups of HIV-infected subjects, including those who were seronegative, untreated virologic controllers [detectable viral load (VL) of <1000 copies/mL], untreated virologic non-controllers [VL > 10,000 copies/mL], and ART-mediated virologic controllers [VL < 75 copies/mL]. A longitudinal analysis of ART-treated subjects was also performed along with regression analysis to determine which biomarkers were associated with and/or predictive of CD4(+) T cell recovery. Suppressive ART was associated with increased levels of classical monocyte subpopulations (CD14(hi)CD16(-)) and decreased levels of non-classical monocyte populations (CD14(dim)CD16(+)). Among peripheral blood mononuclear cells (PBMCs), HO-1 was found to be most highly up-regulated in CD14(+) monocytes after ex vivo stimulation. Neither the levels of monocyte subpopulations nor of HO-1 expression in CD14(+) monocytes were significantly associated with the degree of CD4(+) T cell recovery. Monocyte subpopulations and HO-1 gene expression were, however, restored to normal levels by suppressive ART. These results suggest that the level of circulating monocyte subpopulations and their expression of HO-1 have no evident relationship to CD4(+) T cell recovery after the initiation of ART.

No MeSH data available.


Related in: MedlinePlus

Circulating monocyte frequencies measured at time points early after ART initiation are not predictive of better subsequent CD4+ T cell recovery in ART-treated subjects. Thawed PBMC samples from Early ART Patients (Table 2) were analyzed for cell surface expression of monocyte markers. Regression analysis of CD4+ T cell recovery between time point 1 and time point 2 was performed using the Spearman rank correlation. Rho coefficient (ρ) reveals lack of association between CD4+ T cell recovery and the following parameters measured at ART time point 1: (A) percentage of classical monocytes, (B) percentage of non-classical monocytes, and (C) HO-1 gMFI levels in CD14+ monocytes.
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Figure 4: Circulating monocyte frequencies measured at time points early after ART initiation are not predictive of better subsequent CD4+ T cell recovery in ART-treated subjects. Thawed PBMC samples from Early ART Patients (Table 2) were analyzed for cell surface expression of monocyte markers. Regression analysis of CD4+ T cell recovery between time point 1 and time point 2 was performed using the Spearman rank correlation. Rho coefficient (ρ) reveals lack of association between CD4+ T cell recovery and the following parameters measured at ART time point 1: (A) percentage of classical monocytes, (B) percentage of non-classical monocytes, and (C) HO-1 gMFI levels in CD14+ monocytes.

Mentions: CD4+ T cell recovery was longitudinally assessed in early ART-suppressed cohort (n = 24, Table 2). All subjects achieved durable ART-mediated viral suppression by seven months of treatment. We hypothesized that subjects with higher pro-inflammatory non-classical CD14dimCD16+ monocyte frequencies may experience lower CD4+ T cell gains during suppressive ART (Table 3). We performed regression analysis to determine if classical monocytes or non-classical monocytes measured at a time point early after ART initiation may be predictive of the subsequent rate of CD4+ T cell count gain (cells/mm3/month). There was no strong evidence of a significant association between either the level of classical monocytes (Spearman’s rho ρ = -0.24, P < ns) (Figure 4A) or of non-classical monocytes (Spearman’s rho ρ = -0.069, P < ns) and CD4+ T cell counts (cells/mm3) measured during early or late ART, nor with the subsequent rate of gain in CD4+ T cell count (cells/mm3/month) (Figure 4B).


Levels of circulating myeloid subpopulations and of heme oxygenase-1 do not predict CD4(+) T cell recovery after the initiation of antiretroviral therapy for HIV disease.

Seu L, Ortiz GM, Burt TD, Deeks SG, Martin JN, McCune JM - AIDS Res Ther (2014)

Circulating monocyte frequencies measured at time points early after ART initiation are not predictive of better subsequent CD4+ T cell recovery in ART-treated subjects. Thawed PBMC samples from Early ART Patients (Table 2) were analyzed for cell surface expression of monocyte markers. Regression analysis of CD4+ T cell recovery between time point 1 and time point 2 was performed using the Spearman rank correlation. Rho coefficient (ρ) reveals lack of association between CD4+ T cell recovery and the following parameters measured at ART time point 1: (A) percentage of classical monocytes, (B) percentage of non-classical monocytes, and (C) HO-1 gMFI levels in CD14+ monocytes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4150425&req=5

Figure 4: Circulating monocyte frequencies measured at time points early after ART initiation are not predictive of better subsequent CD4+ T cell recovery in ART-treated subjects. Thawed PBMC samples from Early ART Patients (Table 2) were analyzed for cell surface expression of monocyte markers. Regression analysis of CD4+ T cell recovery between time point 1 and time point 2 was performed using the Spearman rank correlation. Rho coefficient (ρ) reveals lack of association between CD4+ T cell recovery and the following parameters measured at ART time point 1: (A) percentage of classical monocytes, (B) percentage of non-classical monocytes, and (C) HO-1 gMFI levels in CD14+ monocytes.
Mentions: CD4+ T cell recovery was longitudinally assessed in early ART-suppressed cohort (n = 24, Table 2). All subjects achieved durable ART-mediated viral suppression by seven months of treatment. We hypothesized that subjects with higher pro-inflammatory non-classical CD14dimCD16+ monocyte frequencies may experience lower CD4+ T cell gains during suppressive ART (Table 3). We performed regression analysis to determine if classical monocytes or non-classical monocytes measured at a time point early after ART initiation may be predictive of the subsequent rate of CD4+ T cell count gain (cells/mm3/month). There was no strong evidence of a significant association between either the level of classical monocytes (Spearman’s rho ρ = -0.24, P < ns) (Figure 4A) or of non-classical monocytes (Spearman’s rho ρ = -0.069, P < ns) and CD4+ T cell counts (cells/mm3) measured during early or late ART, nor with the subsequent rate of gain in CD4+ T cell count (cells/mm3/month) (Figure 4B).

Bottom Line: We hypothesized that such variation and/or differences in the degree to which these cells expressed the immunoregulatory enzyme, heme oxygenase-1 (HO-1), would be associated with CD4(+) T cell recovery after the initiation of ART.This hypothesis was tested in a cross-sectional study of four groups of HIV-infected subjects, including those who were seronegative, untreated virologic controllers [detectable viral load (VL) of <1000 copies/mL], untreated virologic non-controllers [VL > 10,000 copies/mL], and ART-mediated virologic controllers [VL < 75 copies/mL].Among peripheral blood mononuclear cells (PBMCs), HO-1 was found to be most highly up-regulated in CD14(+) monocytes after ex vivo stimulation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA 94110, USA ; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94110, USA.

ABSTRACT
The level (or frequency) of circulating monocyte subpopulations such as classical (CD14(hi)CD16(-)) and non-classical (CD14(dim)CD16(+)) monocytes varies during the course of HIV disease progression and antiretroviral therapy (ART). We hypothesized that such variation and/or differences in the degree to which these cells expressed the immunoregulatory enzyme, heme oxygenase-1 (HO-1), would be associated with CD4(+) T cell recovery after the initiation of ART. This hypothesis was tested in a cross-sectional study of four groups of HIV-infected subjects, including those who were seronegative, untreated virologic controllers [detectable viral load (VL) of <1000 copies/mL], untreated virologic non-controllers [VL > 10,000 copies/mL], and ART-mediated virologic controllers [VL < 75 copies/mL]. A longitudinal analysis of ART-treated subjects was also performed along with regression analysis to determine which biomarkers were associated with and/or predictive of CD4(+) T cell recovery. Suppressive ART was associated with increased levels of classical monocyte subpopulations (CD14(hi)CD16(-)) and decreased levels of non-classical monocyte populations (CD14(dim)CD16(+)). Among peripheral blood mononuclear cells (PBMCs), HO-1 was found to be most highly up-regulated in CD14(+) monocytes after ex vivo stimulation. Neither the levels of monocyte subpopulations nor of HO-1 expression in CD14(+) monocytes were significantly associated with the degree of CD4(+) T cell recovery. Monocyte subpopulations and HO-1 gene expression were, however, restored to normal levels by suppressive ART. These results suggest that the level of circulating monocyte subpopulations and their expression of HO-1 have no evident relationship to CD4(+) T cell recovery after the initiation of ART.

No MeSH data available.


Related in: MedlinePlus