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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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Related in: MedlinePlus

Changes in the overall and HIV-specific CD8+ T cell subsets during the first two years of infection.The frequency of HIV-specific CD8+ T cells and overall CD8+ T cells expressing each marker or combination of markers are shown for the first two years of life. All infants were infected by 1 month of age. Connected gray lines show individual infants with more than 1 measurement of phenotype (N = 5), one infant had only one time point analyzed for phenotype (B1-334, + symbol).
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pone-0020375-g003: Changes in the overall and HIV-specific CD8+ T cell subsets during the first two years of infection.The frequency of HIV-specific CD8+ T cells and overall CD8+ T cells expressing each marker or combination of markers are shown for the first two years of life. All infants were infected by 1 month of age. Connected gray lines show individual infants with more than 1 measurement of phenotype (N = 5), one infant had only one time point analyzed for phenotype (B1-334, + symbol).

Mentions: Figure 3 shows longitudinal data from early through chronic infection in the overall CD8+ and HIV-specific CD8+ T cell subsets. Since the study specimens were collected at a variety of time-points, we created time intervals of 3–6 months, 7–12 months and 23–24 months post HIV-1 infection to enable quantitative comparisons of overall CD8+ and HIV-specific CD8+ T cell subsets and the description of changes over time (Table 2). HIV-specific CD8+ T cells were highly polarized toward an intermediate, activated phenotype compared to the overall CD8+ T cell subset. The frequency of CD27+CD28− cells was higher in the HIV-specific CD8+ T cell subset (mean 73%, range 41–83) compared to the overall CD8+ T cell subset (27%, range 7.0–48) during the 7–12 month interval (p = 0.018). HLA-DR+ cells were detected at high levels in the HIV-specific CD8+ T cell subset compared to the overall CD8+ subset at 3–6 months (81%, range 45–97 versus 43%, range 35–62, respectively; p = 0.017), 7–12 months (79%, range 45–90 versus 39% range 24–51, respectively; p = 0.005), and 23–24 months post HIV-1 infection (80%, range 68–85 versus 34%, range 32–35%, respectively; p = 0.0032). Similarly, CD95+ cells were detected at a higher frequency in the HIV-specific CD8+ T cell subset compared to the overall CD8+ subset at 3–6 months (92%, range 28–95 versus 56%, range 8.4–78, respectively; p = 0.027), 7–12 months (83%, range 46–91 versus 47%, range 16–63, respectively; p = 0.010), and 23–24 months (88%, range 79–96 versus 47%, range 34–61, respectively; p = 0.030) post HIV-1 infection.


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)

Changes in the overall and HIV-specific CD8+ T cell subsets during the first two years of infection.The frequency of HIV-specific CD8+ T cells and overall CD8+ T cells expressing each marker or combination of markers are shown for the first two years of life. All infants were infected by 1 month of age. Connected gray lines show individual infants with more than 1 measurement of phenotype (N = 5), one infant had only one time point analyzed for phenotype (B1-334, + symbol).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0020375-g003: Changes in the overall and HIV-specific CD8+ T cell subsets during the first two years of infection.The frequency of HIV-specific CD8+ T cells and overall CD8+ T cells expressing each marker or combination of markers are shown for the first two years of life. All infants were infected by 1 month of age. Connected gray lines show individual infants with more than 1 measurement of phenotype (N = 5), one infant had only one time point analyzed for phenotype (B1-334, + symbol).
Mentions: Figure 3 shows longitudinal data from early through chronic infection in the overall CD8+ and HIV-specific CD8+ T cell subsets. Since the study specimens were collected at a variety of time-points, we created time intervals of 3–6 months, 7–12 months and 23–24 months post HIV-1 infection to enable quantitative comparisons of overall CD8+ and HIV-specific CD8+ T cell subsets and the description of changes over time (Table 2). HIV-specific CD8+ T cells were highly polarized toward an intermediate, activated phenotype compared to the overall CD8+ T cell subset. The frequency of CD27+CD28− cells was higher in the HIV-specific CD8+ T cell subset (mean 73%, range 41–83) compared to the overall CD8+ T cell subset (27%, range 7.0–48) during the 7–12 month interval (p = 0.018). HLA-DR+ cells were detected at high levels in the HIV-specific CD8+ T cell subset compared to the overall CD8+ subset at 3–6 months (81%, range 45–97 versus 43%, range 35–62, respectively; p = 0.017), 7–12 months (79%, range 45–90 versus 39% range 24–51, respectively; p = 0.005), and 23–24 months post HIV-1 infection (80%, range 68–85 versus 34%, range 32–35%, respectively; p = 0.0032). Similarly, CD95+ cells were detected at a higher frequency in the HIV-specific CD8+ T cell subset compared to the overall CD8+ subset at 3–6 months (92%, range 28–95 versus 56%, range 8.4–78, respectively; p = 0.027), 7–12 months (83%, range 46–91 versus 47%, range 16–63, respectively; p = 0.010), and 23–24 months (88%, range 79–96 versus 47%, range 34–61, respectively; p = 0.030) post HIV-1 infection.

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