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Phenotypic characterization of HIV-specific CD8+ T cells during early and chronic infant HIV-1 infection.

Slyker JA, John-Stewart GC, Dong T, Lohman-Payne B, Reilly M, Atzberger A, Taylor S, Maleche-Obimbo E, Mbori-Ngacha D, Rowland-Jones SL - PLoS ONE (2011)

Bottom Line: We examined the frequency and phenotype of infant HIV-specific CD8(+) T cells in 7 HIV-infected antiretroviral therapy-naïve infants during the first 2 years of life, using class I HLA tetramers and IFN-γ-ELISPOT.Unlike adults, at 23-24 months post-infection a high frequency of HIV-specific CD8(+) T cells expressed HLA-DR (mean 80%, range 68-85%) and CD95 (mean 88%, range 79-96%), suggesting sustained activation and vulnerability to apoptosis.Despite comparable expansion of HIV-specific CD8(+) T cells of a similar phenotype to adults during early infection, infant T cells failed to contain HIV-1 replication, and remained persistently activated and vulnerable to apoptosis during chronic infection.

View Article: PubMed Central - PubMed

Affiliation: MRC Human Immunology Unit, Oxford University, Oxford, United Kingdom. jslyker@uw.edu

ABSTRACT
Although CD8(+) T cells play an important role in the containment of adult HIV-1 replication, their role in infant HIV-1 infection is not as well understood. Impaired HIV-specific CD8(+) T cell responses may underlie the persistently high viral loads observed in infants. We examined the frequency and phenotype of infant HIV-specific CD8(+) T cells in 7 HIV-infected antiretroviral therapy-naïve infants during the first 2 years of life, using class I HLA tetramers and IFN-γ-ELISPOT. The frequency (0.088-3.9% of CD3(+)CD8(+) cells) and phenotype (CD27(+)CD28(-), CD45RA(+/-), CD57(+/-), HLA-DR(+), CD95(+)) of infant HIV-specific CD8(+) T cells were similar to reports in adults undergoing early infection. Unlike adults, at 23-24 months post-infection a high frequency of HIV-specific CD8(+) T cells expressed HLA-DR (mean 80%, range 68-85%) and CD95 (mean 88%, range 79-96%), suggesting sustained activation and vulnerability to apoptosis. Despite comparable expansion of HIV-specific CD8(+) T cells of a similar phenotype to adults during early infection, infant T cells failed to contain HIV-1 replication, and remained persistently activated and vulnerable to apoptosis during chronic infection.

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Differentiation of infant CD8 T cells during early and chronic infant HIV-1 infection.Dot plots and histograms show representative phenotyping during the first two years of life in subject B1-093, who was HIV-1 RNA positive at birth. Dot plots show A) CD27 and CD28 and B) CD45RA and CD57 staining. HIV-specific CD8+ T cells (gated on tetramer+/CD3+CD8+) are shown as black dot plots overlaid on the overall CD8+ subset (gated on CD3+CD8+), which are shown as density plots in gray. Quadrant statistics are shown below each dot plot, for the overall CD8+ (left diagram) and HIV-specific CD8+ T cell subsets (right diagram). Histograms show C) HLA-DR and D) CD95 staining, the overall CD8+ subset is shown by the solid gray histogram, and the HIV-specific CD8+ T cell subset is overlaid in black outline as an unshaded histogram. Histogram gate percentages are shown above the plots for the overall CD8+, and HIV-specific CD8+ T cell subsets, respectively.
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pone-0020375-g002: Differentiation of infant CD8 T cells during early and chronic infant HIV-1 infection.Dot plots and histograms show representative phenotyping during the first two years of life in subject B1-093, who was HIV-1 RNA positive at birth. Dot plots show A) CD27 and CD28 and B) CD45RA and CD57 staining. HIV-specific CD8+ T cells (gated on tetramer+/CD3+CD8+) are shown as black dot plots overlaid on the overall CD8+ subset (gated on CD3+CD8+), which are shown as density plots in gray. Quadrant statistics are shown below each dot plot, for the overall CD8+ (left diagram) and HIV-specific CD8+ T cell subsets (right diagram). Histograms show C) HLA-DR and D) CD95 staining, the overall CD8+ subset is shown by the solid gray histogram, and the HIV-specific CD8+ T cell subset is overlaid in black outline as an unshaded histogram. Histogram gate percentages are shown above the plots for the overall CD8+, and HIV-specific CD8+ T cell subsets, respectively.

Mentions: Analysis of the overall CD8+ and HIV-specific CD8+ T cell subsets demonstrated a phenotype similar to that observed in adults undergoing acute HIV-1 infection. Figure 2 shows longitudinal CD8+ T cell phenotype of a representative infant infected with HIV-1 in utero. Though the overall CD8+ T cell subset was a homogenous mixture of CD27+CD28+ (early), CD27+CD28− (intermediate) and CD27−CD28− (late) differentiated cells, HIV-specific CD8+ T cells were predominantly CD27+CD28− (Figure 2A). A subset of CD3+CD8+ expressed both CD45RA and CD57, suggesting the generation of terminally differentiated effector cells (Figure 2B). Consistent with their role as effector cells, CD45RA+CD57+ cells expressed high levels of HLA-DR, indicative of activation (data not shown). Both the overall CD8+ and HIV-specific CD8+ T cell subsets contained high frequencies of HLA-DR+ (Figure 2C) and CD95+ cells (Figure 2D).


Phenotypic characterization of HIV-specific CD8+ T cells during early and chronic infant HIV-1 infection.

Slyker JA, John-Stewart GC, Dong T, Lohman-Payne B, Reilly M, Atzberger A, Taylor S, Maleche-Obimbo E, Mbori-Ngacha D, Rowland-Jones SL - PLoS ONE (2011)

Differentiation of infant CD8 T cells during early and chronic infant HIV-1 infection.Dot plots and histograms show representative phenotyping during the first two years of life in subject B1-093, who was HIV-1 RNA positive at birth. Dot plots show A) CD27 and CD28 and B) CD45RA and CD57 staining. HIV-specific CD8+ T cells (gated on tetramer+/CD3+CD8+) are shown as black dot plots overlaid on the overall CD8+ subset (gated on CD3+CD8+), which are shown as density plots in gray. Quadrant statistics are shown below each dot plot, for the overall CD8+ (left diagram) and HIV-specific CD8+ T cell subsets (right diagram). Histograms show C) HLA-DR and D) CD95 staining, the overall CD8+ subset is shown by the solid gray histogram, and the HIV-specific CD8+ T cell subset is overlaid in black outline as an unshaded histogram. Histogram gate percentages are shown above the plots for the overall CD8+, and HIV-specific CD8+ T cell subsets, respectively.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105047&req=5

pone-0020375-g002: Differentiation of infant CD8 T cells during early and chronic infant HIV-1 infection.Dot plots and histograms show representative phenotyping during the first two years of life in subject B1-093, who was HIV-1 RNA positive at birth. Dot plots show A) CD27 and CD28 and B) CD45RA and CD57 staining. HIV-specific CD8+ T cells (gated on tetramer+/CD3+CD8+) are shown as black dot plots overlaid on the overall CD8+ subset (gated on CD3+CD8+), which are shown as density plots in gray. Quadrant statistics are shown below each dot plot, for the overall CD8+ (left diagram) and HIV-specific CD8+ T cell subsets (right diagram). Histograms show C) HLA-DR and D) CD95 staining, the overall CD8+ subset is shown by the solid gray histogram, and the HIV-specific CD8+ T cell subset is overlaid in black outline as an unshaded histogram. Histogram gate percentages are shown above the plots for the overall CD8+, and HIV-specific CD8+ T cell subsets, respectively.
Mentions: Analysis of the overall CD8+ and HIV-specific CD8+ T cell subsets demonstrated a phenotype similar to that observed in adults undergoing acute HIV-1 infection. Figure 2 shows longitudinal CD8+ T cell phenotype of a representative infant infected with HIV-1 in utero. Though the overall CD8+ T cell subset was a homogenous mixture of CD27+CD28+ (early), CD27+CD28− (intermediate) and CD27−CD28− (late) differentiated cells, HIV-specific CD8+ T cells were predominantly CD27+CD28− (Figure 2A). A subset of CD3+CD8+ expressed both CD45RA and CD57, suggesting the generation of terminally differentiated effector cells (Figure 2B). Consistent with their role as effector cells, CD45RA+CD57+ cells expressed high levels of HLA-DR, indicative of activation (data not shown). Both the overall CD8+ and HIV-specific CD8+ T cell subsets contained high frequencies of HLA-DR+ (Figure 2C) and CD95+ cells (Figure 2D).

Bottom Line: We examined the frequency and phenotype of infant HIV-specific CD8(+) T cells in 7 HIV-infected antiretroviral therapy-naïve infants during the first 2 years of life, using class I HLA tetramers and IFN-γ-ELISPOT.Unlike adults, at 23-24 months post-infection a high frequency of HIV-specific CD8(+) T cells expressed HLA-DR (mean 80%, range 68-85%) and CD95 (mean 88%, range 79-96%), suggesting sustained activation and vulnerability to apoptosis.Despite comparable expansion of HIV-specific CD8(+) T cells of a similar phenotype to adults during early infection, infant T cells failed to contain HIV-1 replication, and remained persistently activated and vulnerable to apoptosis during chronic infection.

View Article: PubMed Central - PubMed

Affiliation: MRC Human Immunology Unit, Oxford University, Oxford, United Kingdom. jslyker@uw.edu

ABSTRACT
Although CD8(+) T cells play an important role in the containment of adult HIV-1 replication, their role in infant HIV-1 infection is not as well understood. Impaired HIV-specific CD8(+) T cell responses may underlie the persistently high viral loads observed in infants. We examined the frequency and phenotype of infant HIV-specific CD8(+) T cells in 7 HIV-infected antiretroviral therapy-naïve infants during the first 2 years of life, using class I HLA tetramers and IFN-γ-ELISPOT. The frequency (0.088-3.9% of CD3(+)CD8(+) cells) and phenotype (CD27(+)CD28(-), CD45RA(+/-), CD57(+/-), HLA-DR(+), CD95(+)) of infant HIV-specific CD8(+) T cells were similar to reports in adults undergoing early infection. Unlike adults, at 23-24 months post-infection a high frequency of HIV-specific CD8(+) T cells expressed HLA-DR (mean 80%, range 68-85%) and CD95 (mean 88%, range 79-96%), suggesting sustained activation and vulnerability to apoptosis. Despite comparable expansion of HIV-specific CD8(+) T cells of a similar phenotype to adults during early infection, infant T cells failed to contain HIV-1 replication, and remained persistently activated and vulnerable to apoptosis during chronic infection.

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Related in: MedlinePlus