Human resident memory T cells (TRM) have currently proven to be functionally distinct from circulating T cells. In regards to this, skin T cells can be postulated to age differently from blood-circulating T cells.

A study assessed T-cell density, diversity, and function in individuals of various ages to investigate the immunologic effects of ageing on human skin from two different countries.

The study found that in elderly individuals, skin T cells maintain their numbers, diversity, cytokine production, and antipathogen responses. An increase in epidermal CD49a+ CD8 TRM in elderly individuals was noted in both a Swedish cohort and a Japanese cohort in each independent analysis. Unspecific stimulation showed diminish in IL-17A production from skin T cells in older individuals with an IFNγ-producing potential in the CD8 T-cell compartment after reversal of cell exhaustion. However, the production was maintained of both IL-17A and IFNγ in response to heat-killed S.au and C.alb in the skin T cells of elderly individuals. 

Thus, it was clear that while skin T cells with IL-17A-producing potential decline through ageing, T cells reactive to specific pathogens that are frequent in the skin are presumed to remain in the skin maintaining their capacity of producing IL-17A and IFNγ through ageing. 

The expression of CD49a is closely related to IFNγ production and cytotoxicity in skin T cells. Thus an increase in CD49a+ CD8 TRM in the elderly epidermis indicates the accumulation of antigen-reactive IFNγ-producing TRM cells over decades of pathogen exposures and increased tumorigenesis through ageing.

Skin T cells also maintained a diverse T-cell repertoire into old age, and ~60% of TCR clones in the skin were found as single copies, suggesting a non-local expansion of T-cell clones. 

The relative sizes of the T-cell pools in the blood and skin of young versus elderly individuals were also estimated, which demonstrated that the skin T-cell pool is twice better maintained than that of the blood T-cell pool of elderly individuals. 

The increase in shared clones between the blood and skin of the same individuals was found to be significant in the blood T cells, but not in the skin T cells, indicating a concomitant increase in skin-unique clones with ageing as skin TRM, implying that blood T cells continuously serve as sources of skin-migrating T cells.

The HTS analysis was utilized to compare the T-cell clones of different individuals. The same T-cell clones were found more frequently within the skin of participants aged 80 years or older contrasting to the participants aged younger than 50 years, whilst common clones did not increase in elderly blood. Combining with the results predicting the maintenance of proliferation and cytokine production in skin T cells in reaction to pathogens, these results indicate that T-cell clones reacting with specific antigens that the immune system often encounters in the skin are preferably accumulated in elderly skin and keep their protective function as long-living TRM. 

Summing up the findings, this study indicates that local T-cell immunity in the skin is maintained more efficiently in advanced age than is circulating T-cell memory, which may partially explain clinical observations that systemic are increased in the elderly but not skin infections. 

Source: Commun Biol. 2021 Jan 4;4(1):13. doi: 10.1038/s42003-020-01551-7. PMID: 33398080; PMCID: PMC7782613.