7 Conclusion and Perspectives
In summary, T cell-mediated adaptive immunity is closely associated with T2DM, which is a chronic metabolic inflammatory illness. With the progression of obesity, IR, and gradual elevation of blood glucose levels, innate immunity is activated first, and there is an increase in the number of T cells under macrophage infiltration, differentiation of CD4+ T cells into pro-inflammatory cells, and a decline in the expression of inflammation-suppressing factors. Among the unconventional T cells that play a bridging role between innate and adaptive immunity are natural killer T cells, mucosal constant T cells (MAIT), and γ-δ-T cells126. These cells recognize lipids, small molecule metabolites, specifically modified peptides, and peptide antigens presented on the cell surface through the classical MHC family and are characterized by broad recognition and rapid response127. Both MAIT and adaptive T cells are activated in pre-diabetes, and the inflammatory balance is tipped toward a pro-inflammatory state. A self-amplified chronic pro-inflammatory milieu and the presence of amyloid peptides contribute to the decline in β cell mass and function, ultimately culminating in the development of T2DM. However, the demarcation between T-cell immune activation and exhaustion in the pathogenesis of T2DM remains unclear, as does when T-cell exhaustion begins. These questions need to be addressed in the future to lay the foundation for the development of new immunotherapies.