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

Yuri Hwang, Hee Tae Yu, Dong Hyun Kim, Jiyeon Jang, Hee Young Kim, Insoo Kang, Hyeon Chang Kim, Sungha Park, Won Woo Lee

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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-6Rαlow or high) were examined by in vitro culture and intracellular FACS analysis. Results: CAD patients had higher frequencies of circulating CD8+IL-6Rαlow effector memory (EM) T cells compared with HCs (median frequency; 74.59% vs. 60.09%, p = 0.0158). Expanded CD8+IL-6Rαlow 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-6Rαlow T cells had features of type 1 cytotoxic CD8+ T cells. Conclusions: Our findings suggest the possible involvement of expanded CD8+IL-6Rαlow EM T cells in CAD through their pro-inflammatory and highly cytotoxic capacities.

Original languageEnglish
Pages (from-to)44-51
Number of pages8
JournalAtherosclerosis
Volume249
DOIs
StatePublished - 1 Jun 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Ireland Ltd.

Keywords

  • CD8 T cells
  • Coronary artery disease
  • IL-6 receptor α chain
  • Interleukin-6
  • Type 1 cytotoxic T cells

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