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Journal of Virology, June 2007, p. 5766-5776, Vol. 81, No. 11
0022-538X/07/$08.00+0     doi:10.1128/JVI.00052-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Cytomegalovirus Infection in Gambian Infants Leads to Profound CD8 T-Cell Differentiation

David J. C. Miles,^1* Marianne van der Sande,² David Jeffries,¹ Steve Kaye,³ Jamila Ismaili,⁴ Olubukola Ojuola,⁵ Mariama Sanneh,¹ Ebrima S. Touray,¹ Pauline Waight,⁶ Sarah Rowland-Jones,¹ Hilton Whittle,¹ and Arnaud Marchant⁷

MRC Laboratories Gambia, P.O. Box 273, Banjul, The Gambia,¹ National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands,² Jefferiss Trust Laboratory, Imperial College London, London, United Kingdom,³ I.B.L. Institut Pasteur, Lille, France,⁴ Department of Pediatrics, Bronx Lebanon Hospital Center, 1650 Selwyn Avenue, Bronx, New York 10457,⁵ Immunisation Department, Health Protection Agency Centre for Infections, London, United Kingdom,⁶ Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi, Belgium⁷

Received 9 January 2007/ Accepted 9 March 2007

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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* Corresponding author. Present address: MLW Clinical Research Programme, P.O. Box 30096, Chichiri, Blantyre 3, Malawi. Phone: 265 1 87 6444. Fax: 265 1 87 5774. E-mail: djcm1{at}liverpool.ac.uk

Published ahead of print on 21 March 2007.

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Journal of Virology, June 2007, p. 5766-5776, Vol. 81, No. 11
0022-538X/07/$08.00+0     doi:10.1128/JVI.00052-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

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