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T-cell responses in the elderly rise slowly and contract quickly, finds study

T-cell responses in the elderly rise slowly and contract quickly
Lower induction and early contraction of spike-specific CD4+ T cells in older adults. a, Absolute number of total and AIM+ (CD137+CD154+) CD4+ T cells in blood. Pre, Post1, Post2 and 3 mo represents the sampling point before vaccination, after the first dose, after the second dose and 3 months after the first dose, respectively. b, Frequency of AIM+ and cytokine+ CD4+ T cells. c, Correlation between the percentage of AIM+ CD4+ T cells before and after vaccination. d, Proportions of multiple cytokine-expressing CD4+ T cells after vaccination in adult and older adult group. The blue, orange and gray colors in pie charts depict the production of one, two and more than three cytokines, respectively. e, Correlations between the percentages of AIM+ CD4+ T cells and age of donors. f, MFI of FSC-A in AIM+ CD4+ T cells. In a, b and f, the center line and error bars indicate the median and IQR, respectively. In b, c and e, the dotted line indicates limit of detection (LOD). Statistical comparisons across cohorts were performed using the Mann–Whitney test. Spearman’s rank correlation (rs) was used to identify relationships between two variables, with a straight line drawn by linear regression analysis. For correlation analysis, percentages of AIM+ CD4+ T cells were transformed into logarithmic values. NS, not significant. Blue, red and black characters represent the results of statistical test from adults (n = 107), older adults (n = 109) and both groups (n = 216), respectively. Credit: Nature Aging (2023). DOI: 10.1038/s43587-022-00343-4

The Yoko Hamazaki Laboratory at CiRA has reported that the slower onset of helper T-cell responses in the elderly after COVID-19 vaccinations is associated with lower antibody production, killer T cell activation, and frequency of adverse reactions.

It is well known that immune functions generally decline with age (immunosenescence). However, it is not well understood how and to what extent aging impacts the responsiveness of T-cells—which play a central role in immune responses against and —to in vivo. In this study, the research team aimed to address these questions by taking advantage of the rare opportunity of a massive vaccination campaign, in which large groups of individuals are exposed to an identical antigen to stimulate their immune systems.

A total of 216 , approximately half adults (aged <65 years) and the other half from the elderly population (aged 65 years or older), all of whom were vaccinated against COVID-19 (Pfizer's BNT162b2), were recruited to the study. The Hamazaki group examined the T-cell responses of these individuals after vaccination and assessed how they correlated with antibody production and adverse reactions.

The results showed that the helper T-cell response after vaccination in the elderly was characterized by slow onset but rapid contraction (waning of the immune response). In addition, vaccine-specific helper T-cells collected from the elderly expressed higher levels of PD-1 (programmed cell death-1), a protein that suppresses T-cell activation, suggesting that the response was more likely to be subdued.

Regardless of age, they also found that individuals with a slower onset of the helper T-cell response had lower maximum antibody titers and killer T-cell activation, but were also less likely to experience systemic adverse reactions.

These results suggest that the key to improving vaccine efficacy is to enhance the helper T-cell response and ensure sufficient cytokine production during the initial vaccination. Furthermore, it has become clear that there are not only age differences but also extremely large individual variations in the immune response induced by vaccines.

These results may be useful for developing more effective vaccine formulations for the elderly and other people with declining , as well as adjusting vaccination schedules to better suit individual immune status. Additional data will be collected through long-term observation to determine whether there are any age-related differences in the maintenance of immune memory.

Furthermore, a better understanding of the mechanisms underlying age and individual differences in the immune response will also help to improve other types of immunotherapies and to devise immune aging interventions (immune rejuvenation) in the future.

The results of this study were published online in Nature Aging on January 12, 2023.

More information: Norihide Jo et al, Impaired CD4+ T cell response in older adults is associated with reduced immunogenicity and reactogenicity of mRNA COVID-19 vaccination, Nature Aging (2023). DOI: 10.1038/s43587-022-00343-4

Journal information: Nature Aging
Provided by Kyoto University
Citation: T-cell responses in the elderly rise slowly and contract quickly, finds study (2023, January 13) retrieved 17 June 2024 from
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