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

被引:275
作者
Almanzar, G
Schwaiger, S
Jenewein, B
Keller, M
Herndler-Brandstetter, D
Würzner, R
Schönitzer, D
Grubeck-Loebenstein, B
机构
[1] Austrian Acad Sci, Inst Biomed Aging Res, Div Immunol, A-6020 Innsbruck, Austria
[2] Innsbruck Med Univ, Dept Hyg Microbiol & Social Med, A-6020 Innsbruck, Austria
[3] Cent Inst Blood Transfus, A-6020 Innsbruck, Austria
[4] Dept Immunol, A-6020 Innsbruck, Austria
关键词
D O I
10.1128/JVI.79.6.3675-3683.2005
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 naive (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 CNWpp65(495-503)-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 naive 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 naive 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.
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页码:3675 / 3683
页数:9
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