Cytomegalovirus infection in Gambian infants leads to profound CD8 T-cell differentiation.
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.
Miles
David J C
DJ
MRC Laboratories Gambia, P.O. Box 273, Banjul, The Gambia. djcm1@liverpool.ac.uk
van der Sande
Marianne
M
Jeffries
David
D
Kaye
Steve
S
Ismaili
Jamila
J
Ojuola
Olubukola
O
Sanneh
Mariama
M
Touray
Ebrima S
ES
Waight
Pauline
P
Rowland-Jones
Sarah
S
Whittle
Hilton
H
Marchant
Arnaud
A
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology*; D005260:Female; D005714:Gambia / Q000453:epidemiology; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male