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

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.