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

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Lundberg, AnnaLinköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten (author)

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

Article/chapterEnglish2021

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2021-06-03
BMC,2021
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LIBRIS-ID:oai:DiVA.org:liu-176848
https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-176848URI
https://doi.org/10.1186/s12967-021-02906-2DOI

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Language:English
Summary in:English

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Funding Agencies|Linkoping University; Heart-Lung Foundation, SwedenSwedish Heart-Lung Foundation [20180436]; Swedish Research CouncilSwedish Research CouncilEuropean Commission [2018-03232]; Swedish Grandlodge of Freemasonry [20191209-141318]
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 H2O2. 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 H2O2, 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 mu g, 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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Immunologi inom det medicinska området hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Immunology in the medical area hsv//eng
Coronary artery disease; Chronic coronary syndrome; T cell; Regulatory T cell; Oxidative stress

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Chung, RosannaLinköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten(Swepub:liu)rosch16 (author)
Zeijlon, LouiseLinköpings universitet,Medicinska fakulteten,Avdelningen för diagnostik och specialistmedicin(Swepub:liu)louze03 (author)
Fernström, GustavLinköpings universitet,Medicinska fakulteten,Avdelningen för diagnostik och specialistmedicin(Swepub:liu)n/a (author)
Jonasson, LenaLinköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Kardiologiska kliniken US(Swepub:liu)lenjo59 (author)
Linköpings universitetAvdelningen för diagnostik och specialistmedicin (creator_code:org_t)

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In:Journal of Translational Medicine: BMC19:11479-5876

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