Cytomegalovirus infection in Gambian infants leads to profound CD8 T-cell differentiation |
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Authors: | Miles David J C van der Sande Marianne Jeffries David Kaye Steve Ismaili Jamila Ojuola Olubukola Sanneh Mariama Touray Ebrima S Waight Pauline Rowland-Jones Sarah Whittle Hilton Marchant Arnaud |
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Affiliation: | MRC Laboratories Gambia, P.O. Box 273, Banjul, The Gambia. djcm1@liverpool.ac.uk |
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Abstract: | Cytomegalovirus (CMV) infection is endemic in Gambian infants, with 62% infected by 3 months and 85% by 12 months of age. We studied the CD8 T-cell responses of infants to CMV following primary infection. CMV-specific CD8 T cells, identified with tetramers, showed a fully differentiated phenotype (CD28(-) CD62L(-) CD95(+) perforin(+) granzyme A(+) Bcl-2(low)). Strikingly, the overall CD8 T-cell population developed a similar phenotype following CMV infection, which persisted for at least 12 months. In contrast, primary infection was accompanied by up-regulation of markers of activation (CD45R0 and HLA-D) on both CMV-specific cells and the overall CD8 T-cell population and division (Ki-67) of specific cells, but neither pattern persisted. At 12 months of age, the CD8 T-cell population of CMV-infected infants was more differentiated than that of uninfected infants. Although the subpopulation of CMV-specific cells remained constant, the CMV peptide-specific gamma interferon response was lower in younger infants and increased with age. As the CD8 T-cell phenotype induced by CMV is indicative of immune dysfunction in the elderly, the existence of a similar phenotype in large numbers of Gambian infants raises the question of whether CMV induces a similarly deleterious effect. |
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