1 Introduction
Type 2 diabetes mellitus (T2DM) has become more common with the aging of
the population and changing lifestyles, and in recent years, the
worldwide incidence of T2DM has risen dramatically1.
Many individuals with T2DM also have genetic variation, obesity, and
decreased immune function, which increases the risk of infections,
cardiovascular disorders, and cognitive disorders. These comorbidities
are the main cause of death and disability in individuals with
T2DM2,3. Firstly, genetics and environment are
important factors in the high incidence of T2DM. According to a large
cohort study, mutations in endocrine-related genes(such as Pax6, Hnf1Α,
PDX1) affect the regulation of β cell development and insulin secretion
and are more likely to develop T2DM. In addition, factors such as
smoking and a high-energy diet are also common risks for
T2DM4.
Overweight and obesity are positively associated with the risk of T2DM.
In individuals with obesity, increased adipocytosis promotes the release
of glycerol and free fatty acids as well as macrophage infiltration.
Ongoing chronic inflammation stimulates T cell activation, which
subsequently promotes the onset and development of insulin resistance
(IR)5, and IR and pancreatic β cell dysfunction
frequently work together to cause T2DM6. There is an
important link between chronic inflammation, poor immune response, and
insulin resistance. These findings have prompted researchers to delve
deeper into possible interactions between insulin and T cells. However,
researchers have examined the immune system in T2DM because it is an
inflammatory illness. Many people with T2DM have abnormally high levels
of T-cell reactivity, which correlates adversely with the C-peptide
index7. Further, the pro-inflammatory cytokine
interleukin (IL)-1β promotes β cell apoptosis when released in response
to high glucose induction8, and tumor necrosis factor
(TNF) has been found to exacerbate hyperglycemia in diabetic
rats9. Further studies revealed that TNF-α activates
c-Jun amino-terminal kinases (JNKs) and inhibitor of kappa B kinase
beta(IKKβ)/nuclear factor kappa B (NF-κB) signaling10,
contributing to the inactivation of insulin receptor-associated
pathways. This leads to IR upregulates inhibitor of matrix
metalloproteinases in keratinocytes, and inhibits wound healing during
diabetes11. Therefore, T cell response plays an
important role in promoting T2DM.
The influence of adaptive immunity on T2DM has gained increasing
attention in recent years, and recent studies have indicated that the
number of B -lymphocytes and CD8+ T cells are
considerably higher in individuals with T2DM, whereas the numbers of
total lymphocytes and CD4+T cells are
decreased12. T2DM is characterized by an increase in
inflammatory cytokines such as IFN-γ and IL-6 and a decrease in
anti-inflammatory cytokines such as IL-1013. T2DM and
its complications are caused in part by chronic inflammation owing to
CD4+ T cell abnormalities. In this review, we discuss
the role of different subpopulations of adaptive T cells in obesity and
T2DM and explore the impact of T cell status on T2DM and the potential
for immunotherapy.