Sicilian semi- and supercentenarians: age-related Tγδ cell immunophenotype contributes to longevity trait definition.

The immune system of semi- (from ≥105 to <110 years old) and supercentenarians (≥110 years old), i.e. oldest centenarians, is thought to have characteristics that allow them to reach extreme longevity in relatively healthy status. Thus, we investigated variations of the two principal subsets of Tγδ, Vδ1, and Vδ2, and their functional subsets using the markers defining Tαβ cells, i.e. CD27, CD45RA, in a cohort of 28 women and 26 men (age range 19–110 years), including 11 long-living individuals (from >90 years old to<105 years old), and eight oldest centenarians (≥105 years old), all of them were previously analysed for Tαβ and NK cell immunophenotypes on the same blood sample collected on recruitment day. Naïve Vδ1 and Vδ2 cells showed an inverse relationship with age, particularly significant for Vδ1 cells. Terminally differentiated T subsets (TEMRA) were significantly increased in Vδ1 but not in Vδ2, with higher values observed in the oldest centenarians, although a great heterogeneity was observed. Both naïve and TEMRA Vδ1 and CD8+ Tαβ cell values from our previous study correlated highly significantly, which was not the case for CD4+ and Vδ2. Our findings on γδ TEMRA suggest that these changes are not unfavourable for centenarians, including the oldest ones, supporting the hypothesis that immune ageing should be considered as a differential adaptation rather than a general immune alteration. The increase in TEMRA Vδ1 and CD8+, as well as in NK, would represent immune mechanisms by which the oldest centenarians successfully adapt to a history of insults and achieve longevity. The aim of the present study was to investigate the impact of ageing on the blood levels of the two main Tγδ populations, including various subsets, in a cohort of 54 Sicilian individuals aged between 19 and 110 years (including eight semi- and supercentenarians). This cohort had previously been extensively studied for Tαβ and NK subsets. The results regarding Tγδ, when combined with the previous findings on Tαβ and NK, lend support to the idea that immune ageing should be regarded as a specific adaptation rather than a general immune alteration. In this context, the increase in TEMRA Vδ1 and CD8+ cells, along with NK CD3–CD56+CD16+, could represent immune mechanisms that enable the oldest centenarians to successfully adapt to a lifetime of antigenic challenges and achieve extreme longevity. Graphical Abstract [ABSTRACT FROM AUTHOR]