5 CD8+ T Cells in T2DM
CD8+ T cells are a crucial type of adaptive immune cells that act as key mediators of immunological surveillance and clearance. Abnormal antigens are delivered through MHC class I molecules, where they are degraded to form peptides and delivered to CD8+ T cells91. CD8+ T cells kill cells carrying these abnormal antigens by releasing cytotoxic molecules, such as granzymes and perforins, and cytokines such as IFN-γ and TNF-α92. CD8+ T cell differentiation is mainly determined by antigenic strength, co-stimulatory molecules, and inflammatory cytokines93. In animal models, the accumulation and polarization of macrophages, accompanied by increased numbers of CD8+ T cells and corresponding cytokines, are observed in the AT of HFD-fed mice, promoting an inflammatory state22,94,95. Additionally, the infiltration of adipose CD8+ T cells into adipose tissue precedes macrophage aggregation, and knocking CD8+ T cells decreases adipose tissue inflammation and the number of macrophages, which improves systemic IR22.
In human studies, increased CD8+ T cells in the AT and peripheral blood are strongly associated with IR and hyperglycemia, and CD8+ T cells also increase with age and the onset of diabetes96,97. Furthermore, with the progression of obesity and T2DM, CD8+ T cells expand to varying degrees in the skeletal muscle, liver, kidney, and intestine respectively, and negatively regulate vascular regeneration and function98–102, suggesting a synergistic effect of CD8+ T cells through the release of cytotoxic particles, and inflammatory factors leading to tissue immunopathology. Therefore, CD8+ T cells that promote metabolic tissue infiltration may be a potential therapeutic target for obesity, aging, T2DM, and associated complications, which are important for treating and delaying related metabolic diseases.