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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+ CD8 T-cells are more activated than the overall CD8 T-cell population, but no more so at 24 than 12 months post-diagnosis.A histograms of the expression of Ki-67 in the overall CD8 T-cell population and tetramer+ subpopulation of a representative sample collected 24 months post-diagnosis, with individual value plots indicating proportions of Ki-67+. B scatter plots of the expression of CD45R0 and CD45RA in the overall CD8 T-cell population and tetramer+ subpopulation of a representative sample collected 24 months post-diagnosis, with individual value plots indicating proportions of CD45R0+ cells and the CD45 ratio derived from all samples. C scatter plots of the expression of CD45R0 and HLA-D in the overall CD8 T-cell population and tetramer+ subpopulation of a representative sample collected 24 months post-diagnosis, with individual value plots indicating proportions of HLA-D+ and CD45R0+HLA-D+ cells and the CD45 ratio derived from all samples. Significances indicate differences between both overall and tetramer+ subpopulations. 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-g001: Tetramer+ CD8 T-cells are more activated than the overall CD8 T-cell population, but no more so at 24 than 12 months post-diagnosis.A histograms of the expression of Ki-67 in the overall CD8 T-cell population and tetramer+ subpopulation of a representative sample collected 24 months post-diagnosis, with individual value plots indicating proportions of Ki-67+. B scatter plots of the expression of CD45R0 and CD45RA in the overall CD8 T-cell population and tetramer+ subpopulation of a representative sample collected 24 months post-diagnosis, with individual value plots indicating proportions of CD45R0+ cells and the CD45 ratio derived from all samples. C scatter plots of the expression of CD45R0 and HLA-D in the overall CD8 T-cell population and tetramer+ subpopulation of a representative sample collected 24 months post-diagnosis, with individual value plots indicating proportions of HLA-D+ and CD45R0+HLA-D+ cells and the CD45 ratio derived from all samples. Significances indicate differences between both overall and tetramer+ subpopulations. 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: Markers of activation were identified by flow cytometry and their frequency was compared among tetramer+ cells and the overall CD8 T-cell population. The proportion of cells in mitotic cycle, defined by Ki-67 expression [28], was low in both the tetramer+ subpopulation and the overall CD8 T-cell population and remained low throughout the second year post-diagnosis (Fig 1A).


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+ CD8 T-cells are more activated than the overall CD8 T-cell population, but no more so at 24 than 12 months post-diagnosis.A histograms of the expression of Ki-67 in the overall CD8 T-cell population and tetramer+ subpopulation of a representative sample collected 24 months post-diagnosis, with individual value plots indicating proportions of Ki-67+. B scatter plots of the expression of CD45R0 and CD45RA in the overall CD8 T-cell population and tetramer+ subpopulation of a representative sample collected 24 months post-diagnosis, with individual value plots indicating proportions of CD45R0+ cells and the CD45 ratio derived from all samples. C scatter plots of the expression of CD45R0 and HLA-D in the overall CD8 T-cell population and tetramer+ subpopulation of a representative sample collected 24 months post-diagnosis, with individual value plots indicating proportions of HLA-D+ and CD45R0+HLA-D+ cells and the CD45 ratio derived from all samples. Significances indicate differences between both overall and tetramer+ subpopulations. 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-g001: Tetramer+ CD8 T-cells are more activated than the overall CD8 T-cell population, but no more so at 24 than 12 months post-diagnosis.A histograms of the expression of Ki-67 in the overall CD8 T-cell population and tetramer+ subpopulation of a representative sample collected 24 months post-diagnosis, with individual value plots indicating proportions of Ki-67+. B scatter plots of the expression of CD45R0 and CD45RA in the overall CD8 T-cell population and tetramer+ subpopulation of a representative sample collected 24 months post-diagnosis, with individual value plots indicating proportions of CD45R0+ cells and the CD45 ratio derived from all samples. C scatter plots of the expression of CD45R0 and HLA-D in the overall CD8 T-cell population and tetramer+ subpopulation of a representative sample collected 24 months post-diagnosis, with individual value plots indicating proportions of HLA-D+ and CD45R0+HLA-D+ cells and the CD45 ratio derived from all samples. Significances indicate differences between both overall and tetramer+ subpopulations. 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: Markers of activation were identified by flow cytometry and their frequency was compared among tetramer+ cells and the overall CD8 T-cell population. The proportion of cells in mitotic cycle, defined by Ki-67 expression [28], was low in both the tetramer+ subpopulation and the overall CD8 T-cell population and remained low throughout the second year post-diagnosis (Fig 1A).

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