Expansion of CD8+ T cells lacking the IL-6 receptor α chain in patients with coronary artery diseases (CAD). (June 2016)

• Record Type: Journal Article
• Authors: Hwang, Yuri; Yu, Hee Tae; Kim, Dong-Hyun; Jang, Jiyeon; Kim, Hee Young; Kang, Insoo; Kim, Hyeon Chang; Park, Sungha; Lee, Won-Woo
• Is Part Of: Atherosclerosis. Volume 249(2016)
• Page Start: 44
• Page End: 51
• Publication Date: 2016-06
• Subjects: Coronary artery disease -- Interleukin-6 -- IL-6 receptor α chain -- CD8+ T cells -- Type 1 cytotoxic T cells; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2016.03.038
• Languages: English
• ISSNs: 0021-9150

Abstract

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. Highlights: CD8 + IL-6Rα low T cells are expanded in patients with coronary artery disease (CAD). Plasma IL-6 positively correlates with CD8 + IL-6Rα low T cells in CAD. CD8 + IL-6Rα low T cells have features typical of type 1 cytotoxic CD8 + T cells. The loss of IL-6Rα on CD8 + T cells is induced by the combination of IL-6 and IL-15.