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Phenotypic Changes of Peripheral gamma delta T Cell and Its Subsets in Patients With Coronary Artery Disease

FRONTIERS IN IMMUNOLOGY(2022)

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摘要
Coronary atherosclerotic heart disease (CAD) is a chronic inflammatory cardiovascular disease with high morbidity and mortality. Growing data indicate that many immune cells are involved in the development of atherosclerosis. However, the immunological roles of gamma delta T cells in the initiation and progression of CAD are not fully understood. Here, we used flow cytometry to determine phenotypical changes of gamma delta T cells and their subpopulations in peripheral blood samples collected from 37 CAD patients. The Pearson correlation coefficient was used to analyze the relationship between the clinical parameter (serum LDL-C level) and the changes of immunophenotypes of gamma delta T cells. Our results demonstrated that the frequencies and absolute numbers of total gamma delta T cells and V delta 2(+) T cells were significantly decreased in CAD patients when compared to healthy individuals. However, the proportion of V delta 1(+) T cells was much lower in CAD patients than that of healthy individuals. Most importantly, a significant alteration of the V delta 1/V delta 2 ratio was found in CAD patients. In addition, a series of surface markers that are associated with costimulatory signals (CD28, CD40L, CD80, CD86), activation levels (CD69, CD25, HLA-DR), activating NK cell receptors (NKp30, NKp46, NKG2D) and inhibitory receptors (PD-1, CTLA-4, PD-1, Tim-3) were determined and then analyzed in the total gamma delta T cells, V delta 2(+)T cells and V delta 2(-)T cells of CAD patients and healthy individuals. The data demonstrated that immunological activities of total gamma delta T cells, V delta 2(+)T cells, and V delta 2(-)T cells of CAD patients were much lower than those in healthy individuals. Moreover, we found that there were positive correlations between the serum LDL-C levels and frequencies of CD3(+)gamma delta(+) T cells, CD69(+)V delta 2(+)T cells, NKG2D(+)V delta 2(+)T cells, and NKp46(+)V delta 2(+)T cells. By contrast, there was an inverse correlation between the levels of serum LDL-C and the frequencies of CD69(+)V delta 2(-)T cells and NKp46(+)V delta 2(-)T cells. Accordingly, these findings could help us to better understand the roles of gamma delta T cells in the CAD, and shed light on the development of novel diagnostic techniques and therapeutic strategies by targeting gamma delta T cells for CAD patients.
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关键词
coronary atherosclerotic heart disease, atherosclerosis, NKG2D, gamma delta T cells, V delta 2(+)T cell, V delta 2(-)T cells
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