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