Anti-cytomegalovirus antibody levels stratify human immune profiles across the lifespan

Makiko Watanabe; Lisa Davidson; Patricia Smith; Peter F Castellucio; Mladen Jergovic; Jennifer L Uhrlaub; Megan J Smithey; Lori E Fantry; Brett Dechambre; Rachel C Wilson; Kenneth C Knox; Jie Ren; Raymond P Stowe; George Weinstock; Homer Twigg 3rd; Janko Ž Nikolich

doi:10.1007/s11357-024-01124-0

Anti-cytomegalovirus antibody levels stratify human immune profiles across the lifespan

Geroscience. 2024 Mar 21. doi: 10.1007/s11357-024-01124-0. Online ahead of print.

Authors

Makiko Watanabe^{1

2}, Lisa Davidson^{1

2}, Patricia Smith³, Peter F Castellucio⁴, Mladen Jergovic^{1

2}, Jennifer L Uhrlaub^{1

2}, Megan J Smithey^{1

2}, Lori E Fantry⁵, Brett Dechambre^{5

6}, Rachel C Wilson³, Kenneth C Knox⁷, Jie Ren⁴, Raymond P Stowe⁸, George Weinstock⁹, Homer Twigg 3rd⁴, Janko Ž Nikolich^{10

11}

Affiliations

¹ Department of Immunobiology, University of Arizona College of Medicine-Tucson, Tucson, AZ, USA.
² Arizona Center On Aging, University of Arizona College of Medicine-Tucson, 1501 N. Campbell Ave, P.O. Box 245221, Tucson, AZ, 85724, USA.
³ Division of Pulmonary Medicine, Department of Medicine, Indiana University College of Medicine, Bloomington, IN, USA.
⁴ Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN, USA.
⁵ Division of Infectious Diseases, Department of Medicine, University of Arizona College of Medicine-Tucson, Tucson, AZ, USA.
⁶ Arizona Department of Health Services, Phoenix, AZ, USA.
⁷ Department of Medicine, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA.
⁸ Microgen Laboratories, La Marque, TX, USA.
⁹ Jackson Laboratories, Bar Harbor, ME, USA.
¹⁰ Department of Immunobiology, University of Arizona College of Medicine-Tucson, Tucson, AZ, USA. nikolich@arizona.edu.
¹¹ Arizona Center On Aging, University of Arizona College of Medicine-Tucson, 1501 N. Campbell Ave, P.O. Box 245221, Tucson, AZ, 85724, USA. nikolich@arizona.edu.

PMID: 38512581
DOI: 10.1007/s11357-024-01124-0

Abstract

Human cytomegalovirus (hCMV) is a ubiquitous latent persistent herpesvirus infecting 60-90% of the population worldwide. hCMV carriage in immunocompetent people is asymptomatic; thus, hCMV can be considered a component of normative aging. However, hCMV powerfully modulates many features of the immune, and likely other, systems and organs. Questions remain as to how hCMV carriage affects the human host. We used anti-CMV antibody titers as a stratifying criterion to examine the impact of "intensity" of hCMV infection as a potential biomarker of aging, inflammation, and immune homeostasis in a cohort of 247 participants stratified into younger (21-40 years) and older (> 65 years of age) groups. We showed that anti-CMV antibody titers increased with age and directly correlated to increased levels of soluble tumor necrosis factor (sTNFR) I in younger but not older participants. CD8 + cell numbers were reduced in the older group due to the loss in CD8 + T naïve (Tn) cells. In CMV carriers and, in particular, in anti-CMV Ab-high participants, this loss was mitigated or reversed by an increase in the numbers of CD8 + T effector memory (Tem) and T effector memory reexpressing CD45RA (Temra) cells. Analysis of CD38, HLA-DR, and CD57 expression revealed subset (CD4 or CD8)-specific changes that correlated with anti-CMV Ab levels. In addition, anti-CMV Ab levels predicted anti-CMV CD8 T cell responsiveness to different CMV open reading frames (ORFs) selectively in older participants, which correlated to the transcriptional order of expression of specific CMV ORFs. Implications of these results for the potential predictive value of anti-CMV Ab titers during aging are discussed.

Keywords: CMV; Immune aging; Immune profiles.

Abstract

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