Limits...
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

Prolonged ART results in an increased frequency of classical monocytes. (A) Thawed PBMCs from HIV patients were stained with antibodies recognizing cell-surface and intracellular myeloid markers. Analysis was performed by sequentially gating on live cells, singlets (FSC-A/FSC-H), non-lymphocyte (SSC-A high/FSC-A high), lineage negative (CD3- CD19- CD56-), and HLA-DR and CD11c positive populations. Myeloid cells were further defined by expression of CD14 and CD16 into three subsets (CD14hiCD16-, CD14dimCD16+, and CD14-CD16- cells). Frequencies of CD14hiCD16- classical monocytes (lower right gate), CD14dimCD16+ non-classical monocytes (upper left gate), and CD11c+ CD14-CD16- mDCs (lower left gate) and in relation to the parent myeloid gate were calculated. (B) Column statistics were performed by 1-way ANOVA on patients described in Table 1. Statistical significance is denoted as *p < 0.05, **p < 0.01, and ***p < 0.001. (C) Myeloid subpopulations were measured during pre-ART to post-ART time points from thawed PBMCs of ART-treated subjects (see "pre- ART-suppressed" subjects described in Table 2). Student’s paired t-test was performed and corresponding p values are described.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Prolonged ART results in an increased frequency of classical monocytes. (A) Thawed PBMCs from HIV patients were stained with antibodies recognizing cell-surface and intracellular myeloid markers. Analysis was performed by sequentially gating on live cells, singlets (FSC-A/FSC-H), non-lymphocyte (SSC-A high/FSC-A high), lineage negative (CD3- CD19- CD56-), and HLA-DR and CD11c positive populations. Myeloid cells were further defined by expression of CD14 and CD16 into three subsets (CD14hiCD16-, CD14dimCD16+, and CD14-CD16- cells). Frequencies of CD14hiCD16- classical monocytes (lower right gate), CD14dimCD16+ non-classical monocytes (upper left gate), and CD11c+ CD14-CD16- mDCs (lower left gate) and in relation to the parent myeloid gate were calculated. (B) Column statistics were performed by 1-way ANOVA on patients described in Table 1. Statistical significance is denoted as *p < 0.05, **p < 0.01, and ***p < 0.001. (C) Myeloid subpopulations were measured during pre-ART to post-ART time points from thawed PBMCs of ART-treated subjects (see "pre- ART-suppressed" subjects described in Table 2). Student’s paired t-test was performed and corresponding p values are described.

Mentions: As shown in Figure 1A, three blood myeloid subpopulations were defined by expression of HLA-DR, CD14, CD16, and CD11c: CD14hiCD16- classical monocytes, CD14dimCD16+ non-classical monocytes, and CD11c+ myeloid dendritic cells (mDCs) (Figure 1A, and Additional file1: Figure S1A)[12].


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)

Prolonged ART results in an increased frequency of classical monocytes. (A) Thawed PBMCs from HIV patients were stained with antibodies recognizing cell-surface and intracellular myeloid markers. Analysis was performed by sequentially gating on live cells, singlets (FSC-A/FSC-H), non-lymphocyte (SSC-A high/FSC-A high), lineage negative (CD3- CD19- CD56-), and HLA-DR and CD11c positive populations. Myeloid cells were further defined by expression of CD14 and CD16 into three subsets (CD14hiCD16-, CD14dimCD16+, and CD14-CD16- cells). Frequencies of CD14hiCD16- classical monocytes (lower right gate), CD14dimCD16+ non-classical monocytes (upper left gate), and CD11c+ CD14-CD16- mDCs (lower left gate) and in relation to the parent myeloid gate were calculated. (B) Column statistics were performed by 1-way ANOVA on patients described in Table 1. Statistical significance is denoted as *p < 0.05, **p < 0.01, and ***p < 0.001. (C) Myeloid subpopulations were measured during pre-ART to post-ART time points from thawed PBMCs of ART-treated subjects (see "pre- ART-suppressed" subjects described in Table 2). Student’s paired t-test was performed and corresponding p values are described.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Prolonged ART results in an increased frequency of classical monocytes. (A) Thawed PBMCs from HIV patients were stained with antibodies recognizing cell-surface and intracellular myeloid markers. Analysis was performed by sequentially gating on live cells, singlets (FSC-A/FSC-H), non-lymphocyte (SSC-A high/FSC-A high), lineage negative (CD3- CD19- CD56-), and HLA-DR and CD11c positive populations. Myeloid cells were further defined by expression of CD14 and CD16 into three subsets (CD14hiCD16-, CD14dimCD16+, and CD14-CD16- cells). Frequencies of CD14hiCD16- classical monocytes (lower right gate), CD14dimCD16+ non-classical monocytes (upper left gate), and CD11c+ CD14-CD16- mDCs (lower left gate) and in relation to the parent myeloid gate were calculated. (B) Column statistics were performed by 1-way ANOVA on patients described in Table 1. Statistical significance is denoted as *p < 0.05, **p < 0.01, and ***p < 0.001. (C) Myeloid subpopulations were measured during pre-ART to post-ART time points from thawed PBMCs of ART-treated subjects (see "pre- ART-suppressed" subjects described in Table 2). Student’s paired t-test was performed and corresponding p values are described.
Mentions: As shown in Figure 1A, three blood myeloid subpopulations were defined by expression of HLA-DR, CD14, CD16, and CD11c: CD14hiCD16- classical monocytes, CD14dimCD16+ non-classical monocytes, and CD11c+ myeloid dendritic cells (mDCs) (Figure 1A, and Additional file1: Figure S1A)[12].

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