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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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Tetramer-staining reveals the expansion of HIV-1 specific CD8 T cells during acute infant HIV-1 infection.A) Representative HLA-A29 GP120 tetramer staining from B1-093, who acquired HIV-1 in utero. Plots show cells gated on CD3+ lymphocytes. Frequencies of tetramer-positive cells are provided as a percent of CD3+CD8+ gated cells. B) Tetramer staining from a negative control donor. C) Frequency of tetramer-positive cells, expressed as a percentage of the CD3+CD8+ subset. Colored lines and markers show individual infants, bold dashed line shows a median spline. D) HIV-1 RNA viral load (solid line with squares, left y-axis), ELISPOT HIVSFU/million PBMC (dashed line with circles, right y-axis), and Tetramer+/106 PBMC (HIV-specific CD8+ T cells, dotted line with triangles, right y-axis) are shown for each of the 7 infants. Note, ELISPOT assays were conducted during live cohort follow-up for 1 year, viral load was measured at each study visit over 2 years of follow-up, tetramer staining was performed on all available frozen specimens. Missing values at visits indicate missed visit or specimen not available for assay.
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pone-0020375-g001: Tetramer-staining reveals the expansion of HIV-1 specific CD8 T cells during acute infant HIV-1 infection.A) Representative HLA-A29 GP120 tetramer staining from B1-093, who acquired HIV-1 in utero. Plots show cells gated on CD3+ lymphocytes. Frequencies of tetramer-positive cells are provided as a percent of CD3+CD8+ gated cells. B) Tetramer staining from a negative control donor. C) Frequency of tetramer-positive cells, expressed as a percentage of the CD3+CD8+ subset. Colored lines and markers show individual infants, bold dashed line shows a median spline. D) HIV-1 RNA viral load (solid line with squares, left y-axis), ELISPOT HIVSFU/million PBMC (dashed line with circles, right y-axis), and Tetramer+/106 PBMC (HIV-specific CD8+ T cells, dotted line with triangles, right y-axis) are shown for each of the 7 infants. Note, ELISPOT assays were conducted during live cohort follow-up for 1 year, viral load was measured at each study visit over 2 years of follow-up, tetramer staining was performed on all available frozen specimens. Missing values at visits indicate missed visit or specimen not available for assay.

Mentions: Seven infants provided a median of 4 cryopreserved specimens (range 1–7 specimens) for tetramer staining. Tetramer staining detected HIV-specific CD8+ T cells in all 7 infants. Figure 1A shows an example of tetramer staining in subject B1-093 who was diagnosed with HIV-1 infection at birth. Though this infant had acquired HIV-1 in utero, no responses to the HLA-A29 GP120 epitope were detected by ELISPOT until 3 months of age, at which time 3.9% of CD3+CD8+ T cells were tetramer-positive. There was a decline in cells detected by tetramer in infant B1-093 after 3 months of age, though a discrete population of A29-GP120 specific cells remained discernable at 24 months. The median peak frequency of tetramer staining in the group of infants was 1.5% of CD3+CD8+ cells (range 0.088–3.9%) and declined thereafter (Figure 1C).


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)

Tetramer-staining reveals the expansion of HIV-1 specific CD8 T cells during acute infant HIV-1 infection.A) Representative HLA-A29 GP120 tetramer staining from B1-093, who acquired HIV-1 in utero. Plots show cells gated on CD3+ lymphocytes. Frequencies of tetramer-positive cells are provided as a percent of CD3+CD8+ gated cells. B) Tetramer staining from a negative control donor. C) Frequency of tetramer-positive cells, expressed as a percentage of the CD3+CD8+ subset. Colored lines and markers show individual infants, bold dashed line shows a median spline. D) HIV-1 RNA viral load (solid line with squares, left y-axis), ELISPOT HIVSFU/million PBMC (dashed line with circles, right y-axis), and Tetramer+/106 PBMC (HIV-specific CD8+ T cells, dotted line with triangles, right y-axis) are shown for each of the 7 infants. Note, ELISPOT assays were conducted during live cohort follow-up for 1 year, viral load was measured at each study visit over 2 years of follow-up, tetramer staining was performed on all available frozen specimens. Missing values at visits indicate missed visit or specimen not available for assay.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3105047&req=5

pone-0020375-g001: Tetramer-staining reveals the expansion of HIV-1 specific CD8 T cells during acute infant HIV-1 infection.A) Representative HLA-A29 GP120 tetramer staining from B1-093, who acquired HIV-1 in utero. Plots show cells gated on CD3+ lymphocytes. Frequencies of tetramer-positive cells are provided as a percent of CD3+CD8+ gated cells. B) Tetramer staining from a negative control donor. C) Frequency of tetramer-positive cells, expressed as a percentage of the CD3+CD8+ subset. Colored lines and markers show individual infants, bold dashed line shows a median spline. D) HIV-1 RNA viral load (solid line with squares, left y-axis), ELISPOT HIVSFU/million PBMC (dashed line with circles, right y-axis), and Tetramer+/106 PBMC (HIV-specific CD8+ T cells, dotted line with triangles, right y-axis) are shown for each of the 7 infants. Note, ELISPOT assays were conducted during live cohort follow-up for 1 year, viral load was measured at each study visit over 2 years of follow-up, tetramer staining was performed on all available frozen specimens. Missing values at visits indicate missed visit or specimen not available for assay.
Mentions: Seven infants provided a median of 4 cryopreserved specimens (range 1–7 specimens) for tetramer staining. Tetramer staining detected HIV-specific CD8+ T cells in all 7 infants. Figure 1A shows an example of tetramer staining in subject B1-093 who was diagnosed with HIV-1 infection at birth. Though this infant had acquired HIV-1 in utero, no responses to the HLA-A29 GP120 epitope were detected by ELISPOT until 3 months of age, at which time 3.9% of CD3+CD8+ T cells were tetramer-positive. There was a decline in cells detected by tetramer in infant B1-093 after 3 months of age, though a discrete population of A29-GP120 specific cells remained discernable at 24 months. The median peak frequency of tetramer staining in the group of infants was 1.5% of CD3+CD8+ cells (range 0.088–3.9%) and declined thereafter (Figure 1C).

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.

Show MeSH
Related in: MedlinePlus