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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

CD14+ monocytes are the main site of HO-1 induction after ex vivo CoPP stimulation. Thawed PBMC samples from Early ART Patients (Table 3) (n = 24) were analyzed for cell surface expression of monocyte markers. (A) Scatter plots showing the expression of CD14 and CD16 after monocyte cell culture in PBS (left) and stimulation with CoPP (right) on UpCell™ plates are depicted (B) Histograms representing the fluorescence intensities of HO-1, CD14, CD16, and CD11c in CD14+ monocytes and in CD11c+ mDCs after treatment with saline or CoPP are shown. Thawed PBMCs were cultured with saline or 25 μM CoPP for 48 hours on UpCell™ plates, harvested, and then stained with antibodies recognizing cell-surface and intracellular myeloid markers. Data from a representative subject are shown. (C) CoPP-induced changes in HO-1 among CD14+ monocytes or CD11c+ DCs. The ****symbol represents a p < 0.0001 for differences in culture conditions (saline vs. CoPP).
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Figure 2: CD14+ monocytes are the main site of HO-1 induction after ex vivo CoPP stimulation. Thawed PBMC samples from Early ART Patients (Table 3) (n = 24) were analyzed for cell surface expression of monocyte markers. (A) Scatter plots showing the expression of CD14 and CD16 after monocyte cell culture in PBS (left) and stimulation with CoPP (right) on UpCell™ plates are depicted (B) Histograms representing the fluorescence intensities of HO-1, CD14, CD16, and CD11c in CD14+ monocytes and in CD11c+ mDCs after treatment with saline or CoPP are shown. Thawed PBMCs were cultured with saline or 25 μM CoPP for 48 hours on UpCell™ plates, harvested, and then stained with antibodies recognizing cell-surface and intracellular myeloid markers. Data from a representative subject are shown. (C) CoPP-induced changes in HO-1 among CD14+ monocytes or CD11c+ DCs. The ****symbol represents a p < 0.0001 for differences in culture conditions (saline vs. CoPP).

Mentions: To determine which of the various myeloid subpopulations circulating in HIV-seropositive subjects might be the main producers of HO-1, stimulation experiments were carried out to detect intracellular HO-1 before and after ex vivo induction with Cobalt protoporphyrin IX (CoPP)[9]. At baseline prior to CoPP stimulation, HO-1 expression was higher in the CD14+ monocyte subpopulation than in the CD11c+ mDC population (Figure 2B).


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)

CD14+ monocytes are the main site of HO-1 induction after ex vivo CoPP stimulation. Thawed PBMC samples from Early ART Patients (Table 3) (n = 24) were analyzed for cell surface expression of monocyte markers. (A) Scatter plots showing the expression of CD14 and CD16 after monocyte cell culture in PBS (left) and stimulation with CoPP (right) on UpCell™ plates are depicted (B) Histograms representing the fluorescence intensities of HO-1, CD14, CD16, and CD11c in CD14+ monocytes and in CD11c+ mDCs after treatment with saline or CoPP are shown. Thawed PBMCs were cultured with saline or 25 μM CoPP for 48 hours on UpCell™ plates, harvested, and then stained with antibodies recognizing cell-surface and intracellular myeloid markers. Data from a representative subject are shown. (C) CoPP-induced changes in HO-1 among CD14+ monocytes or CD11c+ DCs. The ****symbol represents a p < 0.0001 for differences in culture conditions (saline vs. CoPP).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: CD14+ monocytes are the main site of HO-1 induction after ex vivo CoPP stimulation. Thawed PBMC samples from Early ART Patients (Table 3) (n = 24) were analyzed for cell surface expression of monocyte markers. (A) Scatter plots showing the expression of CD14 and CD16 after monocyte cell culture in PBS (left) and stimulation with CoPP (right) on UpCell™ plates are depicted (B) Histograms representing the fluorescence intensities of HO-1, CD14, CD16, and CD11c in CD14+ monocytes and in CD11c+ mDCs after treatment with saline or CoPP are shown. Thawed PBMCs were cultured with saline or 25 μM CoPP for 48 hours on UpCell™ plates, harvested, and then stained with antibodies recognizing cell-surface and intracellular myeloid markers. Data from a representative subject are shown. (C) CoPP-induced changes in HO-1 among CD14+ monocytes or CD11c+ DCs. The ****symbol represents a p < 0.0001 for differences in culture conditions (saline vs. CoPP).
Mentions: To determine which of the various myeloid subpopulations circulating in HIV-seropositive subjects might be the main producers of HO-1, stimulation experiments were carried out to detect intracellular HO-1 before and after ex vivo induction with Cobalt protoporphyrin IX (CoPP)[9]. At baseline prior to CoPP stimulation, HO-1 expression was higher in the CD14+ monocyte subpopulation than in the CD11c+ mDC population (Figure 2B).

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