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Maintenance of large subpopulations of differentiated CD8 T-cells two years after cytomegalovirus infection in Gambian infants.

Miles DJ, van der Sande M, Jeffries D, Kaye S, Ojuola O, Sanneh M, Cox M, Palmero MS, Touray ES, Waight P, Rowland-Jones S, Whittle H, Marchant A - PLoS ONE (2008)

Bottom Line: CMV-specific cells identified using tetramers remained more activated and differentiated than the overall CD8 population.Although markers of activation (CD45R0 and HLA-D) declined throughout the first year, HLA-D expression continued to decline during the second year and CD45R0 expression increased slightly.The age-related increase in IFNgamma response observed during the first year continued but was non-significant during the second year, indicating that the rate of functional improvement had slowed substantially.

View Article: PubMed Central - PubMed

Affiliation: MRC Laboratories Gambia, Banjul, The Gambia. djcm1@liverpool.ac.uk

ABSTRACT

Background: In a previously published study, we found that large differentiated subpopulations of CD8 T-cells emerged rapidly after CMV infection in young infants and persisted throughout the following year. Here we describe a follow-up study conducted on the same infants to establish whether the differentiated subpopulations continued through the second year post-infection.

Methodology / principal findings: CMV-specific cells identified using tetramers remained more activated and differentiated than the overall CD8 population. The large subpopulation of differentiated cytotoxic (CD28(-)CD62L(-)Bcl-2(low)CD95(+)perforin(+)) cells that emerged rapidly after infection remained stable after two years. No similar subpopulation was found in CMV-uninfected infants indicating that two years after infection, CMV remained a major factor in driving CD8 T-cell differentiation. Although markers of activation (CD45R0 and HLA-D) declined throughout the first year, HLA-D expression continued to decline during the second year and CD45R0 expression increased slightly. The age-related increase in IFNgamma response observed during the first year continued but was non-significant during the second year, indicating that the rate of functional improvement had slowed substantially. CONCLUSIONS / SIGNIFICANCE: The large differentiated subpopulations of CD8 T-cells that had emerged immediately after CMV infection persisted through the second year post-infection, while levels of activation and functional capacity remained fairly constant.

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Tetramer+ cells are more differentiated than the overall CD8 T-cell population, but there is little change in the relative proportions of the subpopulations in the second year post-diagnosis.A Scatter plots of the expression of CD27 and CD28 gated on all CD8 T-cells and on tetramer+ CD8 T-cells, and individual value plots of the percentages of cells that fell into each of the defined subpopulations within the overall CD8 and tetramer+ populations. B Scatter plots of the expression of CD27 and perforin gated on all CD8 T-cells and on tetramer+ CD8 T-cells, and individual value plots of the percentages of cells that fell into each of the defined subpopulations within the overall CD8 and tetramer+ populations. C Scatter plots of the expression of CD27 and granzyme A gated on all CD8 T-cells and on tetramer+ CD8 T-cells, and individual value plots of the percentages of cells that fell into each of the defined subpopulations within the overall CD8 and tetramer+ populations. Significant differences between sample times are indicated where present. Grey bars indicate means. Significant differences between tetramer+ and overall CD8 T-cell populations are indicated by *p<0.05, **p<0.005 or ***p<0.0005.
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pone-0002905-g002: Tetramer+ cells are more differentiated than the overall CD8 T-cell population, but there is little change in the relative proportions of the subpopulations in the second year post-diagnosis.A Scatter plots of the expression of CD27 and CD28 gated on all CD8 T-cells and on tetramer+ CD8 T-cells, and individual value plots of the percentages of cells that fell into each of the defined subpopulations within the overall CD8 and tetramer+ populations. B Scatter plots of the expression of CD27 and perforin gated on all CD8 T-cells and on tetramer+ CD8 T-cells, and individual value plots of the percentages of cells that fell into each of the defined subpopulations within the overall CD8 and tetramer+ populations. C Scatter plots of the expression of CD27 and granzyme A gated on all CD8 T-cells and on tetramer+ CD8 T-cells, and individual value plots of the percentages of cells that fell into each of the defined subpopulations within the overall CD8 and tetramer+ populations. Significant differences between sample times are indicated where present. Grey bars indicate means. Significant differences between tetramer+ and overall CD8 T-cell populations are indicated by *p<0.05, **p<0.005 or ***p<0.0005.

Mentions: Differentiation was evaluated by stratifying CD8 T-cells into undifferentiated (CD27+CD28+), intermediate (CD27+CD28−) and fully differentiated (CD27−CD28−) subpopulations [30], [32]–[34]. There were consistently more intermediate and fully differentiated cells among the tetramer+ subpopulation than among the overall CD8 T-cell population throughout the second year post-diagnosis (Fig 2A), as there had been throughout the first year.


Maintenance of large subpopulations of differentiated CD8 T-cells two years after cytomegalovirus infection in Gambian infants.

Miles DJ, van der Sande M, Jeffries D, Kaye S, Ojuola O, Sanneh M, Cox M, Palmero MS, Touray ES, Waight P, Rowland-Jones S, Whittle H, Marchant A - PLoS ONE (2008)

Tetramer+ cells are more differentiated than the overall CD8 T-cell population, but there is little change in the relative proportions of the subpopulations in the second year post-diagnosis.A Scatter plots of the expression of CD27 and CD28 gated on all CD8 T-cells and on tetramer+ CD8 T-cells, and individual value plots of the percentages of cells that fell into each of the defined subpopulations within the overall CD8 and tetramer+ populations. B Scatter plots of the expression of CD27 and perforin gated on all CD8 T-cells and on tetramer+ CD8 T-cells, and individual value plots of the percentages of cells that fell into each of the defined subpopulations within the overall CD8 and tetramer+ populations. C Scatter plots of the expression of CD27 and granzyme A gated on all CD8 T-cells and on tetramer+ CD8 T-cells, and individual value plots of the percentages of cells that fell into each of the defined subpopulations within the overall CD8 and tetramer+ populations. Significant differences between sample times are indicated where present. Grey bars indicate means. Significant differences between tetramer+ and overall CD8 T-cell populations are indicated by *p<0.05, **p<0.005 or ***p<0.0005.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2483415&req=5

pone-0002905-g002: Tetramer+ cells are more differentiated than the overall CD8 T-cell population, but there is little change in the relative proportions of the subpopulations in the second year post-diagnosis.A Scatter plots of the expression of CD27 and CD28 gated on all CD8 T-cells and on tetramer+ CD8 T-cells, and individual value plots of the percentages of cells that fell into each of the defined subpopulations within the overall CD8 and tetramer+ populations. B Scatter plots of the expression of CD27 and perforin gated on all CD8 T-cells and on tetramer+ CD8 T-cells, and individual value plots of the percentages of cells that fell into each of the defined subpopulations within the overall CD8 and tetramer+ populations. C Scatter plots of the expression of CD27 and granzyme A gated on all CD8 T-cells and on tetramer+ CD8 T-cells, and individual value plots of the percentages of cells that fell into each of the defined subpopulations within the overall CD8 and tetramer+ populations. Significant differences between sample times are indicated where present. Grey bars indicate means. Significant differences between tetramer+ and overall CD8 T-cell populations are indicated by *p<0.05, **p<0.005 or ***p<0.0005.
Mentions: Differentiation was evaluated by stratifying CD8 T-cells into undifferentiated (CD27+CD28+), intermediate (CD27+CD28−) and fully differentiated (CD27−CD28−) subpopulations [30], [32]–[34]. There were consistently more intermediate and fully differentiated cells among the tetramer+ subpopulation than among the overall CD8 T-cell population throughout the second year post-diagnosis (Fig 2A), as there had been throughout the first year.

Bottom Line: CMV-specific cells identified using tetramers remained more activated and differentiated than the overall CD8 population.Although markers of activation (CD45R0 and HLA-D) declined throughout the first year, HLA-D expression continued to decline during the second year and CD45R0 expression increased slightly.The age-related increase in IFNgamma response observed during the first year continued but was non-significant during the second year, indicating that the rate of functional improvement had slowed substantially.

View Article: PubMed Central - PubMed

Affiliation: MRC Laboratories Gambia, Banjul, The Gambia. djcm1@liverpool.ac.uk

ABSTRACT

Background: In a previously published study, we found that large differentiated subpopulations of CD8 T-cells emerged rapidly after CMV infection in young infants and persisted throughout the following year. Here we describe a follow-up study conducted on the same infants to establish whether the differentiated subpopulations continued through the second year post-infection.

Methodology / principal findings: CMV-specific cells identified using tetramers remained more activated and differentiated than the overall CD8 population. The large subpopulation of differentiated cytotoxic (CD28(-)CD62L(-)Bcl-2(low)CD95(+)perforin(+)) cells that emerged rapidly after infection remained stable after two years. No similar subpopulation was found in CMV-uninfected infants indicating that two years after infection, CMV remained a major factor in driving CD8 T-cell differentiation. Although markers of activation (CD45R0 and HLA-D) declined throughout the first year, HLA-D expression continued to decline during the second year and CD45R0 expression increased slightly. The age-related increase in IFNgamma response observed during the first year continued but was non-significant during the second year, indicating that the rate of functional improvement had slowed substantially. CONCLUSIONS / SIGNIFICANCE: The large differentiated subpopulations of CD8 T-cells that had emerged immediately after CMV infection persisted through the second year post-infection, while levels of activation and functional capacity remained fairly constant.

Show MeSH
Related in: MedlinePlus