Aging and cytomegalovirus infection differentially and jointly affect distinct circulating T cell subsets in humans

The abundance of naive T cells declines substantially with age.

“it is well characterized that the abundance of naive T cells declines substantially with age (Briceño et al., 2016; Qi et al., 2014; Wertheimer et al., 2014).”

Absolute numbers of naive CD4+ T cells in peripheral blood are stable in the elderly, while circulating naive CD8+ T cells progressively decline with age.

“Absolute numbers of naive CD4+ T cells in peripheral blood have been reported to be stable in the elderly. In contrast, circulating naive CD8+ T cells are progressively lost with age”

The age-related expansion of memory and terminally differentiated CD8+ TEMRA populations is largely caused by CMV.

“the expansion of memory and in particular terminally differentiated CD8+ effector cell (TEMRA) populations that is seen with age is largely caused by CMV”

TEMRA T cells are mostly specific for latent viruses such as CMV and EBV, suggesting that nature and chronicity of viral stimulation rather than age drives their functional phenotype.

“As discussed above, these cells are mostly specific for latent viruses, such as CMV and EBV (Newell et al., 2012), suggesting that the nature and chronicity of viral stimulation rather than age drives their functional phenotype”

Aging per se leads only to a relative accumulation of memory cell subsets, linked to the decrease in naïve cell populations.

“Aging per se leads only to a relative accumulation of memory cell subsets, linked to the decrease in naïve cell populations.”

The absolute increase in memory T cells, called memory inflation, is observed only in older people infected by HCMV.

“The absolute increase in memory T cells, called memory inflation, is observed only in older people infected by HCMV (40).”

Inflationary CD8+ cells, after proper activation stimuli, can divide, secrete cytokines, and execute cytolysis, i.e., they are not exhausted.

“Inflationary CD8+ cells, after proper activation stimuli, can divide, secrete cytokines, and execute cytolysis, i.e., they are not exhausted.”

These inflated HCMV-specific memory T cells maintain their efficient effector functions for the lifetime of the individual.

“These inflated HCMV-specific memory T cells maintain their efficient effector functions for the lifetime of the individual (40, 46, 52).”

TEMRA cells do not accumulate in elderly CMV seronegative individuals.

“as TEMRA cells do not accumulate in elderly CMV seronegative individuals (Wertheimer et al. 2014)”

Naïve T cells decline with age even in individuals not infected with CMV.

“considering the age-associated decline of these cells even in those not infected with CMV (Vescovini et al. 2013; Wertheimer et al. 2014).”