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Journal of Virology, March 2005, p. 3675-3683, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3675-3683.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Long-Term Cytomegalovirus Infection Leads to Significant Changes in the Composition of the CD8+ T-Cell Repertoire, Which May Be the Basis for an Imbalance in the Cytokine Production Profile in Elderly Persons

Giovanni Almanzar,1 Susanne Schwaiger,1 Brigitte Jenewein,1 Michael Keller,1 Dietmar Herndler-Brandstetter,1 Reinhard Würzner,2 Diether Schönitzer,3 and Beatrix Grubeck-Loebenstein1*

Immunology Division, Institute for Biomedical Aging Research, Austrian Academy of Sciences,1 Department of Hygiene, Microbiology and Social Medicine, Innsbruck Medical University,2 Central Institute for Blood Transfusion and Immunological Department, Innsbruck, Austria3

Received 13 August 2004/ Accepted 26 October 2004

In spite of the present belief that latent cytomegalovirus (CMV) infection drives CD8+ T-cell differentiation and induces premature immune senescence, no systematic studies have so far been performed to compare phenotypical and functional changes in the CD8+ T-cell repertoire in CMV-infected and noninfected persons of different age groups. In the present study, number, cytokine production, and growth potential of naïve (CD45RA+ CD28+), memory (CD45RA– CD28+), and effector (CD45RA+ CD28– or CD45RA– CD28–) CD8+ T cells were analyzed in young, middle-aged, and elderly clinically healthy persons with a positive or negative CMV antibody serology. Numbers and functional properties of CMVpp65495-503-specific CD8+ T cells were also studied. We demonstrate that aging as well as CMV infection lead to a decrease in the size of the naïve CD8+ T-cell pool but to an increase in the number of CD8+ effector T cells, which produce gamma interferon but lack substantial growth potential. The size of the CD8+ memory T-cell population, which grows well and produces interleukin-2 (IL-2) and IL-4, also increases with aging, but this increase is missing in CMV carriers. Life-long latent CMV infection seems thus to diminish the size of the naïve and the early memory T-cell pool and to drive a Th1 polarization within the immune system. This can lead to a reduced diversity of CD8 responses and to chronic inflammatory processes which may be the basis of severe health problems in elderly persons.

* Corresponding author. Mailing address: Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg, 10, A-6020 Innsbruck, Austria. Phone: 43 512 583919. Fax: 43 512 583918-8. E-mail: Beatrix.Grubeck{at}oeaw.ac.at.

Journal of Virology, March 2005, p. 3675-3683, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3675-3683.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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