Recent animal studies showed T cells have a direct pathogenic role in the development of heart failure (HF). However, which subsets of T cells contribute to human HF pathogenesis and progression remains unclear. We characterized immunologic properties of various subsets of T cells and their clinical implications in human HF. Thirty-eight consecutive patients with newly diagnosed acute HF (21 males, mean age 66 ± 16 years) and 38 healthy control subjects (21 males, mean age 62 ± 12 years) were enrolled. We found that pro-inflammatory mediators, including CRP, IL-6 and IP-10 and the frequencies of CD57+ T cells in the CD4+ T cell population were significantly elevated in patients with acute HF compared to control subjects. A functional analysis of T cells from patients with acute HF revealed that the CD4+CD57+ T cell population exhibited a higher frequency of IFN-γ- and TNF-α- producing cells compared to the CD4+CD57− T cell population. Furthermore, the frequency of CD4+CD57+ T cells at baseline and its elevation at the six-month follow-up were significantly related with the development of cardiovascular (CV) events, which were defined as CV mortality, cardiac transplantation, or rehospitalization due to HF exacerbation. In conclusion, CD4+CD57+ senescent T cells showed more inflammatory features and polyfunctionality and were associated with clinical outcome in patients with acute HF. More detailed study for senescent T cells might offer new opportunities for the prevention and treatment of human HF.
Bibliographical noteFunding Information:
Some of the contents from this article has been presented as an abstract in the Jay N. Cohn New Investigator Award: Basic Science Finalist Session of the 22nd annual scientific meeting of the Heart Failure Society of America (September 15–18, 2018, Nashville, TN) (Journal of Cardiac Failure 2018; 24(8S):S2-S3). This research was supported by a Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT, & Future Planning (NRF-2018R1C1B6005448), by a grant of the Korean Society of Cardiometabolic Syndrome, by a grant of the Korean Society for Transplantation (2016, 2017) and by the KAIST Future Systems Healthcare Project from the Ministry of Science and ICT. The funders played no role in study design, data collection, data analysis, decision to publish, or preparation of the manuscript. The authors declare no competing interests.
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