Abstract
Objective
To study the role of the programmed death-1 (PD-1)/programmed death-1 ligand 1 (PD-L1)
coinhibitory pathway in regulating CD4+CD28− T cells, and to explore the association of soluble PD-L1 (sPD-L1) in the development
of T2DM with atherosclerotic macrovascular diseases.
Methods
The percentage of CD4+CD28− T lymphocyte subsets from peripheral blood mononuclear cells (PBMCs) and the expression
of PD-1/PD-L1 on lymphocytes were analyzed by immunostaining and flow cytometry, respectively.
The serum levels of sPD-L1 and IFN-γ were determined by ELISA system. T cell proliferation
was determined by cocultivation and WST-8 incorporation.
Results
In 125 T2DM patients and 48 healthy donors, CD4+CD28− T cells from patients with T2DM expressed higher PD-1 than that of the cells from
healthy individuals, and the proliferation response of CD4+CD28− T cells could be enhanced by advanced glycation end products (AGEs). The levels of
sPD-L1 in patients were also much higher than those of healthy donors, and the increase
was displayed in an exacerbation-dependent manner in the T2DM with atherosclerotic
macrovascular patients especially with acute coronary syndrome (ACS). The production
of sPD-L1 was significantly positively correlated with the level of IFN-γ and could
enhance T cell proliferation.
Conclusion
Both the upregulation of PD-1 and the increase of sPD-L1 were closely associated with
the severity of diabetic atherosclerotic macrovascular diseases. sPD-L1 may contribute
to the continuous T cell activation and development of diabetic macrovascular diseases.
Abbreviations:
T2DM (Type 2 Diabetes), CVD (cardiovascular disease), PD-1 (Programmed death-1), PD-L1 (Programmed death-1 ligand 1), AGEs (advanced glycation end products), ACS (acute coronary syndrome), DC (dendritic cells), AS (atherosclerotic macrovascular complications), IMT (intima-media thickness), ELISA (Enzyme-linked immunosorbent assay), UA (unstable angina), HC (healthy controls)Keywords
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Article info
Publication history
Published online: February 11, 2013
Accepted:
December 9,
2012
Received:
April 7,
2012
Identification
Copyright
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
