Skin T cells maintain their diversity and functionality in the elderly

Abstract

Recent studies have highlighted that human resident memory T cells (TRM) are functionally distinct from circulating T cells. Thus, it can be postulated that skin T cells age differently from blood-circulating T cells. We assessed T-cell density, diversity, and function in individuals of various ages to study the immunologic effects of aging on human skin from two different countries. No decline in the density of T cells was noted with advancing age, and the frequency of epidermal CD49a+ CD8 TRM was increased in elderly individuals regardless of ethnicity. T-cell diversity and antipathogen responses were maintained in the skin of elderly individuals but declined in the blood. Our findings demonstrate that in elderly individuals, skin T cells maintain their density, diversity, and protective cytokine production despite the reduced T-cell diversity and function in blood. Skin resident T cells may represent a long-lived, highly protective reservoir of immunity in elderly people.

Skin Aging, Cellular Senescence and Natural Polyphenols

“…Consistently, an increased expression of programmed death protein 1 (PD-1) on CD4+ T cells has been shown in the skin and peripheral blood populations of these cells in older adults, which renders them more susceptible to inhibition [ 170 ]. Furthermore, no decline in the density of T cells in human skin was found with advancing age, and the frequency of epidermal CD49a+ CD8+ resident memory T cells was increased in elderly individuals regardless of the ethnicity and decline in T cell diversity and function in blood [ 171 ]. Moreover, in contrast to the dermis, the epidermis showed a significant decrease in the CD4+/CD8+ ratio by aging ( p = 0.0349, r = −0.4736), suggesting CD8+ T cell accumulation in this layer.…”

“…In addition, as discussed above, an increased expression of PD-1 on CD4+ T cells was also observed in cutaneous aging [ 170 ]. Nevertheless, recent data show that the frequency of epidermal CD49a+ CD8+ resident memory T cells was increased in elderly individuals, regardless of ethnicity, and the overall cutaneous T cell density, diversity and protective cytokine production appear to be maintained in aged skin [ 171 ].…”

Skin-Resident Memory T Cells: Pathogenesis and Implication for the Treatment of Psoriasis

“…The T RM phenotype of the malignant cells in CTCL is related to the clinical manifestation of well-demarcated lesions, suggesting that the sessile property of T RM also exists in humans [24]. In vitro experiments suggest skin T RM maintain the production of IL-17A and IFN-γ in reaction with pathogen challenges through aging [59]. Using transcriptomic and functional data, human T RM are found to abolish their senescent phenotype and survive for over 10 years in specific circumstances [46], replicating the longevity of T RM in humans.…”

Maintenance of the virus-specific CD8+ T-cell repertoire: Implications for vaccine strategies

“…Several studies have suggested that TCR repertoire diversity in tissues is maintained for longer periods of time than in blood, which would be in line with the relative longevity of TRM cells. Koguchi-Yoshioka et al showed a reduction in TCR repertoire diversity, T-cell density and cytokine production of total T cells in the blood of older adults as compared to younger individuals [441]. In contrast, T-cell repertoire diversity, T-cell density and cytokine production of T cells in the skin were suggested to be maintained with age, as they showed comparable results between older and younger adults.…”