Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Jun;17(6):986-92.
doi: 10.1128/CVI.00455-09. Epub 2010 Apr 28.

Cytomegalovirus infection- and age-dependent changes in human CD8+ T-cell cytokine expression patterns

Benjamin Faist  1 , Bernhard Fleischer, Marc Jacobsen
Affiliations

Cytomegalovirus infection- and age-dependent changes in human CD8+ T-cell cytokine expression patterns

Benjamin Faist et al. Clin Vaccine Immunol. 2010 Jun.

Abstract

T cells are strongly affected by immune aging, a phenomenon that leads to increased susceptibility to infections and decreased vaccination efficacy in elderly individuals. Cytomegalovirus (CMV) infection induces vigorous T-cell immune responses in humans and is thought to be a driving force of immune aging. In the present study we analyzed CMV-induced quantitative and qualitative differences in the cytokine-expressing T-cell repertoire from individuals of different age groups after in vitro stimulation. The CMV pp65 peptide pool and the superantigen Staphylococcus enterotoxin B (SEB) induced higher proportions of CD8+ effector T cells expressing gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and granulocyte-macrophage colony-stimulating factor in the oldest study group, while only SEB induced increased responses in the middle-aged study group. Notably, CMV-specific multiple cytokine expression patterns revealed higher proportions of IFN-gamma- and TNF-alpha-coexpressing CD8+ T cells exclusively in the oldest study group. These qualitative differences were absent in SEB-induced CD8+ effector T cells, although quantitative differences were detected. We report age-dependent qualitative changes in CMV-specific CD8+ T-cell cytokine patterns which are biocandidate markers of immune exhaustion in elderly individuals.

PubMed Disclaimer

Figures

FIG. 1.
FIG. 1.
T-cell population proportions and CMV-specific serum IgG levels from different age groups. The ratios of naïve (CD45RA+ CCR7+) versus nonnaïve (CD45RA− CCR7+, CD45RA− CCR7−, and CD45RA− CCR7−) cell proportions for CD4+ (a) and CD8+ (b) T cells are shown. Median values and standard deviations (in parentheses) of absolute numbers are given for naïve T cells (upper row) and nonnaïve T cells (lower row) for each study group. (c) CMV-specific serum IgG levels are shown. The dashed line indicates the upper limit of the serum test. For this analysis 20 donors (5 young, 8 middle-aged, and 9 old) were included. Box plots and error bars represent the 5, 25, 50, 75, and 95 percentiles. Different colors indicate the young study group (white), the middle-aged study group (light gray), and the old study group (dark gray). Nominal two-sided P values for the Mann-Whitney U-test are indicated (***, P < 0.001).
FIG. 2.
FIG. 2.
SEB-induced and CMV-specific single-cytokine expression levels in CD4+ and CD8+ central memory T cells from different age groups. Box plots indicate SEB-induced (a and b) and CMV peptide pool-induced (c and d) proportions of IFN-γ (upper left graphs), TNF-α (upper right graphs), GM-CSF (lower left graphs), and IL-2 (lower right graphs) for CD4+ central memory T cells (a and c) as well as for CD8+ central memory T cells (b and d). Box plots and error bars represent the 5, 25, 50, 75, and 95 percentiles. Different hatchings mark each cytokine. Different colors indicate the young study group (white), the middle-aged study group (light gray), and the old study group (dark gray).
FIG. 3.
FIG. 3.
CD4+ and CD8+ effector T-cell single-cytokine expression levels after SEB-induced and CMV-specific in vitro stimulation for different age groups. Box plots indicate SEB-induced (a and b) and CMV peptide pool-induced (c and d) proportions of IFN-γ (upper left graphs), TNF-α (upper right graphs), GM-CSF (lower left graphs), and IL-2 (lower right graphs) for CD4+ effector T cells (a and c) as well as for CD8+ effector T cells (b and d). Box plots and error bars represent the 5, 25, 50, 75, and 95 percentiles. Different hatchings mark each cytokine. Different colors indicate the young study group (white), the middle-aged study group (light gray), and the old study group (dark gray). Nominal two-sided P values for the Mann-Whitney U-test are indicated (*, P < 0.05; ***, P < 0.001).
FIG. 4.
FIG. 4.
Cytokine expression patterns induced by SEB or CMV in CD4+ and CD8+ effector T cells. Line and scatter plots indicate mean expression levels and standard deviations (y axes) of distinct cytokine coexpression pattern (x axes) for CD4+ effector T cells (a and c) and CD8+ effector T cells (b and d) stimulated with SEB (a and b) or CMV peptide pool (c and d). Lines connect mean values (circles) of the same study group (additionally indicated by the color: young study group [white], middle-aged study group [light gray], and old study group [dark gray]). For evaluation of the CMV-specific pattern 8 individuals from the young study group, 10 individuals from the middle-aged study group, and 9 individuals from the old study group who had more than 20 cytokine-positive effector T cells were included. Proportions of each cytokine coexpression subset were calculated relative to the number of cells expressing at least one of the analyzed cytokines: IFN-γ, TNF-α, GM-CSF, and IL-2. Boxes below the graphs enclose triple-, double-, or single-cytokine expression subsets. Nominal two-sided P values for the t test are indicated (*, P < 0.05; **, P < 0.01).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bunde, T., A. Kirchner, B. Hoffmeister, D. Habedank, R. Hetzer, G. Cherepnev, S. Proesch, P. Reinke, H. D. Volk, H. Lehmkuhl, and F. Kern. 2005. Protection from cytomegalovirus after transplantation is correlated with immediate early 1-specific CD8 T cells. J. Exp. Med. 201:1031-1036. - PMC - PubMed
    1. Candore, G., G. Di Lorenzo, M. Melluso, D. Cigna, A. T. Colucci, M. A. Modica, and C. Caruso. 1993. γ-Interferon, interleukin-4 and interleukin-6 in vitro production in old subjects. Autoimmunity 16:275-280. - PubMed
    1. Darrah, P. A., D. T. Patel, P. M. De Luca, R. W. Lindsay, D. F. Davey, B. J. Flynn, S. T. Hoff, P. Andersen, S. G. Reed, S. L. Morris, M. Roederer, and R. A. Seder. 2007. Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nat. Med. 13:843-850. - PubMed
    1. Fagiolo, U., A. Cossarizza, E. Scala, E. Fanales-Belasio, C. Ortolani, E. Cozzi, D. Monti, C. Franceschi, and R. Paganelli. 1993. Increased cytokine production in mononuclear cells of healthy elderly people. Eur. J. Immunol. 23:2375-2378. - PubMed
    1. Fletcher, J. M., M. Vukmanovic-Stejic, P. J. Dunne, K. E. Birch, J. E. Cook, S. E. Jackson, M. Salmon, M. H. Rustin, and A. N. Akbar. 2005. Cytomegalovirus-specific CD4+ T cells in healthy carriers are continuously driven to replicative exhaustion. J. Immunol. 175:8218-8225. - PubMed