Atherosclerosis 249 (2016) 44-51


 

Expansion of CD8+ T cells lacking the IL-6 receptor a

chain in patients with coronary artery diseases (CAD)

Yuri Hwang a, Hee Tae Yu b, Dong-Hyun Kim c, d, Jiyeon Jang a, Hee Young Kim a, e, Insoo Kang f, Hyeon Chang Kim g, Sungha Park b, **, Won-Woo Lee a, c, d, e, h, *


 

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 a chain (IL-6Ra), a cytokine known to play a key role in cardiovascular diseases.

Methods: The expression of IL-6Ra 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-6Ra (CD8+IL-6Ralow or high) were examined by in vitro culture and intracellular FACS analysis.

Results: CAD patients had higher frequencies of circulating CD8+IL-6Ralow effector memory (EM) T cells compared with HCs (median frequency; 74.59% vs. 60.09%, p ¼ 0.0158). Expanded CD8+IL-6Ralow T cells
positively correlated with the frequency of senescent, cytotoxic CD8+CD57þ T cells (r ¼ 0.6655, p < 0.0001) and plasma IL-6 level (r ¼ 0.3995, p ¼ 0.0432) in CAD patients. Loss of IL-6Ra expression on CD8+ T cells was induced by the combination of IL-6 and IL-15 with accompanying TCR-independent proliferation (p ¼ 0.0101). Moreover, these CD8+IL-6Ralow T cells had features of type 1 cytotoxic CD8+ T cells.

Conclusions: Our findings suggest the possible involvement of expanded CD8+IL-6Ralow EM T cells in CAD through their pro-inflammatory and highly cytotoxic capacities.