Oxidative stress response in regulatory and conventional T cells: a comparison between patients with chronic coronary syndrome and healthy subjects

• Published in: Journal of translational medicine Vol. 19; no. 1; pp. 1 - 241
• Main Authors: Lundberg, Anna K, Chung, Rosanna W. S, Zeijlon, Louise, Fernström, Gustav, Jonasson, Lena
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 03.06.2021; BioMed Central; BMC
• Subjects: Acute coronary syndromes; Antioxidants; Apoptosis; Arteriosclerosis; Atherosclerosis; Cardiovascular disease; CD25 antigen; CD4 antigen; Cell death; Cellular stress response; Chronic coronary syndrome; Chronic illnesses; Coronary artery disease; Coronary heart disease; Coronary vessels; Development and progression; Flow cytometry; Gene expression; Health aspects; Hydrogen peroxide; Leukocytes (mononuclear); Low density lipoprotein; Lymphocytes; Lymphocytes T; Oxidants; Oxidative stress; Peripheral blood mononuclear cells; Physiological aspects; Regulatory T cell; T cell; T cells; Thioredoxin; Sweden; Oxidative stress; Chronic coronary syndrome; Coronary artery disease; T cell; Regulatory T cell
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-021-02906-2

Abstract Background Inflammation and oxidative stress form a vicious circle in atherosclerosis. Oxidative stress can have detrimental effects on T cells. A unique subset of CD4 + T cells, known as regulatory T (T reg ) cells, has been associated with atheroprotective effects. Reduced numbers of T reg cells is a consistent finding in patients with chronic coronary syndrome (CCS). However, it is unclear to what extent these cells are sensitive to oxidative stress. In this pilot study, we tested the hypothesis that oxidative stress might be a potential contributor to the T reg cell deficit in CCS patients. Methods Thirty patients with CCS and 24 healthy controls were included. T reg (CD4 + CD25 + CD127 − ) and conventional T (CD4 + CD25 − , T conv ) cells were isolated and treated with increasing doses of H 2 O 2 . Intracellular ROS levels and cell death were measured after 2 and 18 h, respectively. The expression of antioxidant genes was measured in freshly isolated T reg and T conv cells. Also, total antioxidant capacity (TAC) was measured in fresh peripheral blood mononuclear cells, and oxidized (ox) LDL/LDL ratios were determined in plasma. Results At all doses of H 2 O 2, T reg cells accumulated more ROS and exhibited higher rates of death than their T conv counterparts, p < 0.0001. T reg cells also expressed higher levels of antioxidant genes, including thioredoxin and thioredoxin reductase-1 (p < 0.0001), though without any differences between CCS patients and controls. T conv cells from CCS patients were, on the other hand, more sensitive to oxidative stress ex vivo and expressed more thioredoxin reductase-1 than T conv cells from controls, p < 0.05. Also, TAC levels were lower in patients, 0.97 vs 1.53 UAE/100 µg, p = 0.001, while oxLDL/LDL ratios were higher, 29 vs 22, p = 0.006. Conclusion T reg cells isolated from either CCS patients or healthy controls were all highly sensitive to oxidative stress ex vivo. There were signs of oxidant-antioxidant imbalance in CCS patients and we thus assume that oxidative stress may play a role in the reduction of T reg cells in vivo.