Research Paper Volume 15, Issue 10 pp 3939—3966

Circulating immune cell phenotypes are associated with age, sex, CMV, and smoking status in the Framingham Heart Study offspring participants

Yuan Fang1, , Margaret F. Doyle2, , Jiachen Chen1, , Jesse Mez3,4,5, , Claudia L. Satizabal4,5,6, , Michael L. Alosco3,4, , Wei Qiao Qiu3,7,8, , Kathryn L. Lunetta1, , Joanne M. Murabito5,9,10, ,

  • 1 Boston University School of Public Health, Department of Biostatistics, Boston, MA 02118, USA
  • 2 University of Vermont, Larner College of Medicine, Department of Pathology and Laboratory Medicine, Burlington, VT 05405, USA
  • 3 Boston University Chobanian and Avedisian School of Medicine, Boston University Alzheimer’s Disease Research Center and CTE Center, Boston, MA 02118, USA
  • 4 Boston University Chobanian and Avedisian School of Medicine, Department of Neurology, Boston, MA 02118, USA
  • 5 Framingham Heart Study, National Heart, Lung, and Blood Institute and Boston University Chobanian and Avedisian School of Medicine, Framingham, MA 01702, USA
  • 6 University of Texas Health Science Center at San Antonio, Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, San Antonio, TX 78229, USA
  • 7 Boston University Chobanian and Avedisian School of Medicine, Department of Psychiatry, Boston, MA 02118, USA
  • 8 Boston University Chobanian and Avedisian School of Medicine, Department of Pharmacology and Experimental Therapeutics, Boston, MA 02118, USA
  • 9 Boston University Chobanian and Avedisian School of Medicine, Department of Medicine, Boston, MA 02118, USA
  • 10 Boston Medical Center, Department of Adult Primary Care, Boston, MA 02119, USA

Received: January 20, 2023       Accepted: April 17, 2023       Published: April 27, 2023
How to Cite
This article has been corrected. See Correction. Aging (Albany NY). 2023; 15:7855-7856 .  PMID: 37580144

Copyright: © 2023 Fang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Understanding the composition of circulating immune cells with aging and the underlying biologic mechanisms driving aging may provide molecular targets to slow the aging process and reduce age-related disease. Utilizing cryopreserved cells from 996 Framingham Heart Study (FHS) Offspring Cohort participants aged 40 and older (mean 62 years, 48% female), we report on 116 immune cell phenotypes including monocytes, T-, B-, and NK cells and their subtypes, across age groups, sex, cytomegalovirus (CMV) exposure groups, smoking and other cardiovascular risk factors. The major cellular differences with CMV exposure were higher Granzyme B+ cells, effector cells, and effector-memory re-expressing CD45RA (TEMRA) cells for both CD4+ and CD8+. Older age was associated with lower CD3+ T cells, lower naïve cells and naïve/memory ratios for CD4+ and CD8+. We identified many immune cell differences by sex, with males showing lower naïve cells and higher effector and effector memory cells. Current smokers showed lower pro-inflammatory CD8 cells, higher CD8 regulatory type cells and altered B cell subsets. No significant associations were seen with BMI and other cardiovascular risk factors. Our cross-sectional observations of immune cell phenotypes provide a reference to further the understanding of the complexity of immune cells in blood, an easily accessible tissue.


FHS: Framingham Heart Study; CMV: cytomegalovirus; HRS: Health and Retirement Study; ARIP: age-related immune phenotype; NK: natural killer; PBMCs: peripheral blood mononuclear cells; CV: coefficients of variation; Tn: naïve; Teff: T effector; Tem: T effector memory; Tcm: T central memory; Th1: T helper type 1; Tc1: cytotoxic T cells type 1; BMI: body-mass index; CVD: cardiovascular disease; AF: atrial fibrillation; SBP: systolic blood pressure; TC: total cholesterol; HDL: high-density lipoprotein; LOD: limit of detection; FDRs: false discovery rates.