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).