Senescent T Cells Predict the Development of Hyperglycemia in Humans

Abstract

Senescent T cells have been implicated in chronic inflammatory and cardiovascular diseases. In this study, we explored the relationship between senescent T cells and glycemic status in a cohort of 805 participants by investigating the frequency of CD57(+) or CD28(null) senescent T cells in peripheral blood. Participants with normal glucose tolerance (NGT) with follow-up data (N = 149) were included to determine whether hyperglycemia (prediabetes or type 2 diabetes) developed during followup (mean 2.3 years). CD8(+) CD57(+) and CD8+ CD28(null) T-cell frequencies were significantly higher in prediabetes and type 2 diabetes compared with NGT. Increased CD57(+) or CD28(null) cells in the CD8(+) T-cell subset were independently associated with hyperglycemia. Furthermore, among participants with baseline NGT, the frequency of CD8(+) CD57(+) T cells was an independent predictor of hyperglycemia development. Immunofluorescent analyses confirmed that CD8(+) CD57(+) T-cell infiltration was increased in visceral adipose tissue of patients with prediabetes or type 2 diabetes compared with those with NGT. Our data suggest that increased frequency of senescent CD8(+) T cells in the peripheral blood is associated with development of hyperglycemia.