title: Aging disturbs the balance between effector and regulatory CD4+ T cells.
abstract: Healthy aging requires an optimal balance between pro-inflammatory and anti-inflammatory immune responses. Although CD4+ T cells play an essential role in many immune responses, few studies have directly assessed the effect of aging on the balance between effector T (Teff) cells and regulatory T (Treg) cells. Here, we determined if and how aging affects the ratio between Treg and Teff cells. Percentages of both naive Treg (nTreg; CD45RA+CD25(int)FOXP3(low)) and memory Treg (memTreg; CD45RA-CD25(high)FOXP3(high)) cells were determined by flow cytometry in peripheral blood samples of healthy individuals of various ages (20-84 years). Circulating Th1, Th2 and Th17 effector cells were identified by intracellular staining for IFN-γ, IL-4 and IL-17, respectively, upon in vitro stimulation with PMA and calcium ionophore. Whereas proportions of nTreg cells declined with age, memTreg cells increased. Both Th1 and Th2 cells were largely maintained in the circulation of aged humans, whereas Th17 cells were decreased. Similar to memTreg cells, the 3 Teff subsets resided primarily in the memory CD4+ T cell compartment. Overall, Treg/Teff ratios were increased in the memory CD4+ T cell compartment of aged individuals when compared to that of young individuals. Finally, the relative increase of memTreg cells in elderly individuals was associated with poor responses to influenza vaccination. Taken together, our findings imply that aging disturbs the balance between Treg cells and Teff cells.
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: k.s.m.van.der.geest@umcg.nl.
authors.forename: Kornelis S M
authors.initials: KS
authors.lastname: van der Geest
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Wayel H
authors.initials: WH
authors.lastname: Abdulahad
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Tete
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Pedro G
authors.initials: PG
authors.lastname: Lorencetti
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Gerda
authors.initials: G
authors.lastname: Horst
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Nicolaas A
authors.initials: NA
authors.lastname: Bos
authors.affiliation: Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Bart-Jan
authors.initials: BJ
authors.lastname: Kroesen
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Brouwer
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Annemieke M H
authors.initials: AM
authors.lastname: Boots
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D055815:Young Adult
chemical_list: D007252:Influenza Vaccines
keywords: Aging; Regulatory T lymphocytes; Th1 cells; Th17 cells; Th2 cells; Vaccination