CD28 and type 2 diabetes mellitus: Glucotoxicity- and lipotoxicity-induced local production of cytokines and chemokines in pancreatic β-cells and insulin-sensitive tissues including adipose tissue and liver initiate the inflammation associated with T2DM.[31] Pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and chemokines released from tissues may recruit and regulate the differentiation and activation of immune cells, triggering the progression of local inflammation.[9,32] Importantly, senescent (CD28 − CD57+) CD8 + T cells are highly inflammatory.