Cytomegalovirus Infection Reduces Telomere Length of the Circulating T Cell Pool

Short telomeres of circulating leukocytes are a risk factor for age-related diseases, such as atherosclerosis, but the exact mechanisms generating variations in telomere length are unknown. We hypothesized that induction of differentiated T cells during chronic CMV infection would affect T cell telo...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2010-04, Vol.184 (7), p.3417-3423
Main Authors: van de Berg, Pablo J. E. J, Griffiths, Stephen J, Yong, Si-La, Macaulay, Richard, Bemelman, Frederike J, Jackson, Sarah, Henson, Sian M, ten Berge, Ineke J. M, Akbar, Arne N, van Lier, Rene A. W
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Antiviral Agents - therapeutic use
Cell Differentiation - immunology
Cell Separation
Cytomegalovirus Infections - genetics
Cytomegalovirus Infections - immunology
Cytomegalovirus Infections - pathology
DNA, Viral - blood
Flow Cytometry
Fluorescent Antibody Technique
Ganciclovir - therapeutic use
Humans
In Situ Hybridization, Fluorescence
Kidney Transplantation - adverse effects
Kidney Transplantation - immunology
Middle Aged
Polymerase Chain Reaction
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - pathology
T-Lymphocytes - immunology
T-Lymphocytes - pathology
Telomere - pathology
Telomere - virology
Viremia - drug therapy
Young Adult
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Summary:Short telomeres of circulating leukocytes are a risk factor for age-related diseases, such as atherosclerosis, but the exact mechanisms generating variations in telomere length are unknown. We hypothesized that induction of differentiated T cells during chronic CMV infection would affect T cell telomere length. To test this, we measured the amount of differentiated T cells and telomere length of lymphocytes during primary CMV infection as well as CMV-seropositive and -seronegative healthy individuals. After primary CMV infection, we observed an increase in highly differentiated cells that coincided with a steep drop in telomere length. Moreover, we found in a cohort of 159 healthy individuals that telomere shortening was more rapid in CMV-seropositive individuals and correlated with the amount of differentiated T cells in both CD4(+) T cells and CD8(+) T cells. Finally, we found that telomere length measured in blood leukocytes is correlated with lymphocyte telomere length. Thus, CMV infection induces a strong decrease in T cell telomere length, which can be explained by changes in the composition of the circulating lymphocyte pool.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.0903442