Yuri Hwang1, Hee Tae Yu2, Dong-Hyun Kim3, Jiyeon Jang1, Hee Young Kim4, Insoo Kang5, Hyeon Chang Kim6, Sungha Park7, Won-Woo Lee8. 1. Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea. 2. Division of Cardiology, Severance Cardiovascular Hospital and Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, South Korea. 3. Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea; BK21Plus Biomedical Science Project, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea. 4. Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea; Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea. 5. Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA. 6. Cardiovascular and Metabolic Diseases Etiology Research Center and Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, South Korea. 7. Division of Cardiology, Severance Cardiovascular Hospital and Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: shpark0530@yuhs.ac. 8. Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea; BK21Plus Biomedical Science Project, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea; Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea; Ischemic/Hypoxic Disease Institute, and Institute of Infectious Diseases, Seoul National University College of Medicine, Seoul National University Hospital Biomedical Research Institute, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea. Electronic address: wonwoolee@snu.ac.kr.
Abstract
BACKGROUND AND AIMS: The pathogenesis of coronary artery disease (CAD) is closely associated with chronic inflammatory processes. CD8(+) T cells are a key participant in the pathogenesis of atherosclerosis, the major cause of CAD; however, it remains unclear which CD8(+) T-cell subset is responsible. We investigated the immunological features of CD8(+) T cells expressing low and high levels of the IL-6 receptor α chain (IL-6Rα), a cytokine known to play a key role in cardiovascular diseases. METHODS: The expression of IL-6Rα on CD8(+) T cells and its association with plasma levels of soluble components of the IL-6/IL-6Rs as well as with clinical parameters were analyzed using FACS analysis and ELISA of CAD patients and age-matched healthy controls (HCs). Immunological characteristics of CD8(+) T cells expressing low and high levels of IL-6Rα (CD8(+)IL-6Rα(low or high)) were examined by in vitro culture and intracellular FACS analysis. RESULTS: CAD patients had higher frequencies of circulating CD8(+)IL-6Rα(low) effector memory (EM) T cells compared with HCs (median frequency; 74.59% vs. 60.09%, p = 0.0158). Expanded CD8(+)IL-6Rα(low) T cells positively correlated with the frequency of senescent, cytotoxic CD8(+)CD57(+) T cells (r = 0.6655, p < 0.0001) and plasma IL-6 level (r = 0.3995, p = 0.0432) in CAD patients. Loss of IL-6Rα expression on CD8(+) T cells was induced by the combination of IL-6 and IL-15 with accompanying TCR-independent proliferation (p = 0.0101). Moreover, these CD8(+)IL-6Rα(low) T cells had features of type 1 cytotoxic CD8(+) T cells. CONCLUSIONS: Our findings suggest the possible involvement of expanded CD8(+)IL-6Rα(low) EM T cells in CAD through their pro-inflammatory and highly cytotoxic capacities.
BACKGROUND AND AIMS: The pathogenesis of coronary artery disease (CAD) is closely associated with chronic inflammatory processes. CD8(+) T cells are a key participant in the pathogenesis of atherosclerosis, the major cause of CAD; however, it remains unclear which CD8(+) T-cell subset is responsible. We investigated the immunological features of CD8(+) T cells expressing low and high levels of the IL-6 receptor α chain (IL-6Rα), a cytokine known to play a key role in cardiovascular diseases. METHODS: The expression of IL-6Rα on CD8(+) T cells and its association with plasma levels of soluble components of the IL-6/IL-6Rs as well as with clinical parameters were analyzed using FACS analysis and ELISA of CAD patients and age-matched healthy controls (HCs). Immunological characteristics of CD8(+) T cells expressing low and high levels of IL-6Rα (CD8(+)IL-6Rα(low or high)) were examined by in vitro culture and intracellular FACS analysis. RESULTS: CAD patients had higher frequencies of circulating CD8(+)IL-6Rα(low) effector memory (EM) T cells compared with HCs (median frequency; 74.59% vs. 60.09%, p = 0.0158). Expanded CD8(+)IL-6Rα(low) T cells positively correlated with the frequency of senescent, cytotoxic CD8(+)CD57(+) T cells (r = 0.6655, p < 0.0001) and plasma IL-6 level (r = 0.3995, p = 0.0432) in CAD patients. Loss of IL-6Rα expression on CD8(+) T cells was induced by the combination of IL-6 and IL-15 with accompanying TCR-independent proliferation (p = 0.0101). Moreover, these CD8(+)IL-6Rα(low) T cells had features of type 1 cytotoxic CD8(+) T cells. CONCLUSIONS: Our findings suggest the possible involvement of expanded CD8(+)IL-6Rα(low) EM T cells in CAD through their pro-inflammatory and highly cytotoxic capacities.
Authors: Elizabeth A Bonney; Ann Howard; Kendall Krebs; Kelly Begin; Kelsey Veilleux; Natalia I Gokina Journal: Reprod Sci Date: 2017-01-19 Impact factor: 3.060
Authors: Jee-Seon Shim; Bo Mi Song; Jung Hyun Lee; Seung Won Lee; Ji Hye Park; Dong Phil Choi; Myung Ha Lee; Kyoung Hwa Ha; Dae Jung Kim; Sungha Park; Won-Woo Lee; Hyeon Chang Kim Journal: Epidemiol Health Date: 2017-04-01
Authors: Lindsey E Padgett; Huy Q Dinh; Runpei Wu; Dalia E Gaddis; Daniel J Araujo; Holger Winkels; Anh Nguyen; Coleen A McNamara; Catherine C Hedrick Journal: Arterioscler Thromb Vasc Biol Date: 2020-10-15 Impact factor: 10.514