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.