2 T Cells in T2DM
Activation of the T cells is a characteristic of persistent inflammation. However, early studies on the immune system in T2DM focused on innate immunity, particularly macrophages. In individuals with T2DM and obesity, there is evidence of decreased NK cell activity14, increased neutrophil apoptosis, decreased chemotaxis and phagocytosis, and predominance of M1-type macrophages with an inflammatory phenotype15,16, which increases the risk of infection with tuberculosis and human immunodeficiency virus17. In addition, neutrophil and eosinophil levels were significantly decreased in T2DM patients18, and obese mice lacking eosinophils exhibited impaired glucose tolerance and insulin resistance19. However, increasing attention has been focused on adaptive immunity, mainly on T cells. Adaptive immune cells mainly refer to T cells that mediate cellular immunity and B cells that mediate humoral immunity. Functional T cell subpopulations are required for B cell activation and development into plasma cells20,21, suggesting that T cell components may change first in the early stage of antigen stimulation.
T-cell receptors are activated by recognizing complexes formed by CD8 with major histocompatibility complex (MHC) class I molecules, and CD4 with MHC class II molecules on antigen-presenting cells (APC)21. Depending on the cell surface differentiation antigens and their functions, CD4+ T cells and CD8+ T cells are the two primary subsets of T lymphocytes. Mice continuously fed an HFD had a higher proportion of CD8+ T cells in the adipose tissue, whereas CD4+ T cells and Tregs were consistently decreased, which began to reverse after 30 weeks22. Therefore, T cell activation during obesity may be mainly characterized by CD8 hypersecretion, after which T cells may enter a state of exhaustion. Different from T1DM, CD8+T cells gradually accumulate in the metabolic tissues of T2DM during the progression of obesity and chronic inflammation. CD8+T cells secrete monocyte chemoattractant protein-1 and interferon-inducible protein-10 and kill abnormal cells22. By contrast, T1DM-activated CD8+ T cells are generated by autoimmune progenitor cells that target and attack insulin-producing pancreatic β cells23. CD4+ T cells are an important regulatory factor subpopulation of T lymphocytes, and can generally be categorized into pro-inflammatory and anti-inflammatory Th cells based on their functional characteristics and secreted cytokines (Figure 1).