Critical immune cells replaced by suboptimal versions in older adulthood

Good news! Towards a fountain of youth! Are older adults becoming like newborns again in some respects of their immune system?

"... Now, in a study ... researchers have examined the difference in killer T cells in newborns, school-aged children, adults, and adults 60 years and over, to understand how age affects our immunity to influenza viruses. ...

The researchers found that the number of total killer T cells was lowest in newborns, increased in children, and peaked in adulthood. Whereas influenza-virus-specific killer T cells were lowest in newborns and children, peaked in adults and decreased in older adults. ...

They performed gene expression analysis on cells categorized by age and found that influenza-specific killer T cells in newborns and children were genetically similar to those seen in older adults. But markers associated with maintaining immune control, anti-inflammatory cytokines and controlling T cell differentiation were highly expressed in adult influenza-specific T cells, less pronounced in children and older adults, and absent in newborns. ..."

From the abstract:

"CD8+ T cells provide robust antiviral immunity, but how epitope-specific T cells evolve across the human lifespan is unclear. Here we defined CD8+ T cell immunity directed at the prominent influenza epitope HLA-A*02:01-M158–66 (A2/M158) across four age groups at phenotypic, transcriptomic, clonal and functional levels. We identify a linear differentiation trajectory from newborns to children then adults, followed by divergence and a clonal reset in older adults. Gene profiles in older adults closely resemble those of newborns and children, despite being clonally distinct. Only child-derived and adult-derived A2/M158+CD8+ T cells had the potential to differentiate into highly cytotoxic epitope-specific CD8+ T cells, which was linked to highly functional public T cell receptor (TCR)αβ signatures. Suboptimal TCRαβ signatures in older adults led to less proliferation, polyfunctionality, avidity and recognition of peptide mutants, although displayed no signs of exhaustion. These data suggest that priming T cells at different stages of life might greatly affect CD8+ T cell responses toward viral infections."

Immune cells replaced by suboptimal versions in older adulthood "Researchers investigating how specialized immune cells called killer T cells [CD8+ or cytotoxic T cells] change over the course of our lives have found that, in older age, these cells are replaced by less effective versions that struggle to fight viral invaders. The world-first discovery improves our understanding of age-related immunity and may lead to improved vaccines and therapies tailored to different age groups."

Newborn and child-like molecular signatures in older adults stem from TCR shifts across human lifespan (open access)

Fig. 1: Age-related changes in A2/M158+CD8+ T cell frequencies and phenotypes.