title: Expansion of CD8(+) T cells lacking the IL-6 receptor α chain in patients with coronary artery diseases (CAD).
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Hwang
authors.affiliation: Division of Cardiology, Severance Cardiovascular Hospital and Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Hee Tae
authors.initials: HT
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea.
authors.forename: Jiyeon
authors.initials: J
authors.lastname: Jang
authors.affiliation: 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.
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Insoo
authors.initials: I
authors.lastname: Kang
authors.affiliation: Cardiovascular and Metabolic Diseases Etiology Research Center and Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Hyeon Chang
authors.initials: HC
authors.lastname: Kim
authors.affiliation: Division of Cardiology, Severance Cardiovascular Hospital and Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: shpark0530@yuhs.ac.
authors.forename: Sungha
authors.initials: S
authors.lastname: Park
authors.affiliation: 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.
authors.forename: Won-Woo
authors.initials: WW
authors.lastname: Lee
mesh_terms: D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D002469:Cell Separation; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation; D019409:Interleukin-15 / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D019947:Receptors, Interleukin-6 / Q000235:genetics* / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000378:metabolism
chemical_list: C569274:IL15 protein, human; C508600:IL6 protein, human; C508603:IL6R protein, human; D019409:Interleukin-15; D015850:Interleukin-6; D019947:Receptors, Interleukin-6
keywords: CD8(+) T cells; Coronary artery disease; IL-6 receptor α chain; Interleukin-6; Type 1 cytotoxic T cells