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J Gerontol A Biol Sci Med Sci. 2015 Aug;70(8):917-23. doi: 10.1093/gerona/glu128. Epub 2015 Apr 7.

CCR4+ Regulatory T Cells Accumulate in the Very Elderly and Correlate With Superior 8-Year Survival.

Author information

1
Department of Internal Medicine II, Centre for Medical Research, University of Tübingen, Tübingen, Germany. evelyna.derhovanessian@biontech.de.
2
Department of Gerontology and Geriatrics and.
3
Department of Internal Medicine, Section of Gerontology and Geriatrics, VU University Medical Centre, Amsterdam, the Netherlands.
4
Department of Internal Medicine II, Centre for Medical Research, University of Tübingen, Tübingen, Germany.
5
Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, the Netherlands.
6
Department of Gerontology and Geriatrics and Netherlands Consortium for Health Aging, Leiden University Medical Centre, Leiden, the Netherlands.

Abstract

CD4(+) regulatory T cells (Tregs) are a distinct population of T cells involved in maintaining peripheral tolerance to self-antigens. Several studies have shown increased frequency and number of Tregs in the elderly. Whether such an increase has any clinical relevance has not been addressed. Here, we have analyzed circulating Tregs in 114 donors between the ages of 18 and 89 years and assessed their implications for survival of the very elderly. In line with previously published data, we observed higher proportions of Tregs in the elderly. Expression of chemokine receptor 4 (CCR4) by Tregs has been shown to characterize antigen-primed activated Tregs with immediate suppressive function. Thus we further analyzed Tregs expressing or lacking this chemokine receptor. There were more CCR4(+) and CCR4(-) Tregs in the elderly than the young. Finally, using a subset of 48 elderly donors participating in the Leiden 85-plus study we documented that people with greater median frequencies of CCR4(+) Tregs enjoyed a better 8-year survival rate than those with lower frequencies of these cells. Our data, demonstrating for the first time a positive correlation between increased frequency of Tregs and survival in the elderly, imply an increasing importance of controlling inappropriate immune responses and inflammation as we grew old.

KEYWORDS:

Cytomegalovirus; Elderly; Mortality; Tregs

PMID:
25852090
DOI:
10.1093/gerona/glu128
[Indexed for MEDLINE]

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