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.