γδ T cell exhaustion is associated with obesity in individuals with type 2 diabetes.

Abstract

Obesity is a major factor driving immune exhaustion in adaptive immune cells, yet its effect on the exhaustion of peripheral circulating innate γδ T cells in individuals with type 2 diabetes (T2D) remains poorly understood. In this study, we recruited 54 individuals with clinically diagnosed T2D and 30 age- and sex-matched healthy donors. We assessed peripheral blood immune cell phenotypes using flow cytometry. Compared with healthy controls, individuals with T2D showed a significant reduction in the proportion of circulating innate-like γδ T cells. Furthermore, exhaustion markers, including PD-1, Tim-3, and TIGIT, were markedly elevated on γδ T cells from T2D participants. Importantly, obesity positively correlated with the co-expression of PD-1 and TIGIT, as well as PD-1 and Tim-3, on γδ T cells. Together, these findings indicate that obesity may exacerbate the exhaustion of circulating γδ T cells in T2D, highlighting a potential link between metabolic dysregulation and innate immune dysfunction.