Lifelong CMV infection improves immune defense in old mice by broadening the mobilized TCR repertoire against third-party infection, 2018, Nikolich

Andy · Jul 9, 2018

Obviously based on results from mice, so take any claims with a pinch of salt.

Significance
Epidemiological studies have shown a correlation between CMV infection and immune system aging, especially in elderly populations. It remains unclear whether CMV infection is a key driver of, or simply a factor associated with, aging of the immune system. We show that aging in the presence of lifelong CMV infection improves T cell immunity in old animals by broadening the immune response to a different pathogen. Animals that have aged with CMV are able to recruit novel T cells into these immune responses that are present in, but not utilized in, animals aging without CMV. These data squarely challenge the premise that CMV is solely detrimental to the aging of the adaptive immune system.

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.
Click to expand...

Paywalled at http://www.pnas.org/content/early/2018/06/26/1719451115

Article about the study

Our immune system is at its peak when we’re young, but after a certain age, it declines and it becomes more difficult for our bodies to fight off new infections.

“That’s why older people are more susceptible to infections than younger people,” explained Dr. Janko Nikolich-Žugich, co-director of the University of Arizona Center on Aging and chairman of the Department of Immunobiology at the UA College of Medicine – Tucson.

In search of a way to rejuvenate the immune system of older adults, Nikolich-Žugich and Megan Smithey began researching cytomegalovirus, or CMV. The virus, which is usually contracted at a young age, affects more than half of all individuals. Because there is no cure, the virus is carried for life and is particularly prevalent in older adults.

“CMV doesn’t usually cause outward symptoms, but we still have to live with it every day since there’s no cure,” said Smithey, a member of the UA Center on Aging and research assistant professor specializing in immunobiology. “Our immune system always will be busy in the background dealing with this virus.”
Click to expand...

https://uanews.arizona.edu/story/virus-may-boost-not-weaken-our-immune-systems

Log in or Sign up

Lifelong CMV infection improves immune defense in old mice by broadening the mobilized TCR repertoire against third-party infection, 2018, Nikolich

Andy Committee Member

Share This Page

Log in or Sign up

Lifelong CMV infection improves immune defense in old mice by broadening the mobilized TCR repertoire against third-party infection, 2018, Nikolich

Andy Committee Member

Share This Page

Useful Searches