title: CCR4+ Regulatory T Cells Accumulate in the Very Elderly and Correlate With Superior 8-Year Survival.
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.
authors: Department of Internal Medicine II, Centre for Medical Research, University of Tübingen, Tübingen, Germany. evelyna.derhovanessian@biontech.de.
authors: Evelyna
authors: E
authors: Derhovanessian
authors: Department of Gerontology and Geriatrics and.
authors: Sijia
authors: S
authors: Chen
authors: Department of Internal Medicine, Section of Gerontology and Geriatrics, VU University Medical Centre, Amsterdam, the Netherlands.
authors: Andrea B
authors: AB
authors: Maier
authors: Department of Internal Medicine II, Centre for Medical Research, University of Tübingen, Tübingen, Germany.
authors: Karin
authors: K
authors: Hähnel
authors: Department of Gerontology and Geriatrics and.
authors: Anton J M
authors: AJ
authors: de Craen
authors: Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, the Netherlands.
authors: Helene
authors: H
authors: Roelofs
authors: Department of Gerontology and Geriatrics and Netherlands Consortium for Health Aging, Leiden University Medical Centre, Leiden, the Netherlands.
authors: Rudi
authors: R
authors: Westendorp
authors: Department of Internal Medicine II, Centre for Medical Research, University of Tübingen, Tübingen, Germany.
authors: Graham
authors: G
authors: Pawelec
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D002097:C-Reactive Protein / Q000032:analysis; D003586:Cytomegalovirus Infections / Q000276:immunology*; D006801:Humans; D008875:Middle Aged; D054398:Receptors, CCR4 / Q000032:analysis*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
chemical_list: C515354:CCR4 protein, human; D054398:Receptors, CCR4; D002097:C-Reactive Protein
keywords: Cytomegalovirus; Elderly; Mortality; Tregs