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Lifelong CMV infection improves immune defense in old mice by broadening the mobilized TCR repertoire against third-party infection.


Maximus Peto’s Commentary

This group reports that, contrary to what one might expect from other reports of CMV infection, mice with murine CMV showed an apparently superior (by some measures) immune response to Listeria monocytogenes. I see Janko is the last author on this paper.


Lifelong CMV infection improves immune defense in old mice by broadening the mobilized TCR repertoire against third-party infection.
Proc Natl Acad Sci U S A. 2018 Jul 17;115(29):E6817-E6825.
Smithey MJ, Venturi V, Davenport MP, Buntzman AS, Vincent BG, Frelinger JA, Nikolich-Žugich J
DOI: 10.1073/pnas.1719451115
PubMed publication date (edat): 7/4/2018

Abstract

Lifelong interactions between host and the ubiquitous and persistent cytomegalovirus (CMV) have been proposed to contribute to the age-related decline in immunity. Prior work from us and others found some support for that idea, yet evidence that this led to increased vulnerability to other infections was not obtained. Moreover, evidence has accumulated that CMV infection can be beneficial to immune defense in young/adult mice and humans, dominantly via enhanced innate immunity. Here, we describe an unexpected impact of murine CMV (MCMV) upon the T cell response of old mice to Listeria monocytogenes expressing the model antigen, OVA (Lm-OVA). Single-cell sequencing of the OVA-specific CD8 T cell receptor β (TCRβ) repertoire of old mice demonstrated that old MCMV-infected mice recruited many diverse clonotypes that afforded broad and often more efficient recognition of antigenic peptide variants. This stood in contrast to old control mice, which exhibited strong narrowing and homogenization of the elicited repertoire. High-throughput sequencing of the total naïve CD8 TCRβ repertoire showed that many of these diverse OVA-specific clonotypes were present in the naïve CD8 repertoire of mice in all groups (adult, old control, and old MCMV+) yet were only recruited into the Lm-OVA response in MCMV+ old mice. These results have profound implications for our understanding of T cell immunity over a life span and suggest that our coevolution with CMV may include surprising, potentially positive impacts on adaptive heterologous immunity in late life.

PMID: 29967140
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055168/

Maximus Peto

Max Peto is a longevity researcher and founder of Long Life Labs. A biochemist by training, he studies the biochemistry of aging and longevity and has worked with research organizations such as SENS Research Foundation, Methuselah Foundation, BioAge Labs, Life Extension Foundation, and Ichor Therapeutics. His work at Long Life Labs is focused on empowering people to understand and manage the most critical factors for better health and longer life.

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