Abstract 11982: Circulating Invariant Natural Killer T Cells are Decreased in Patients With Chronic Heart Failure

Abstract

Objective: Inflammatory mediators play a crucial role in the development of chronic heart failure (HF). Invariant natural killer T (iNKT) cells, a unique subset of T lymphocytes, which recognize glycolipid antigens and secrete a large amount of T helper (Th) 1/Th2 cytokines on activation, function as immunomodulatory cells in the various pathological processes. We have demonstrated that iNKT cells have a protective role against the development of left ventricular (LV) remodeling and failure after myocardial infarction in mice. However, it remains unclear whether iNKT cells are involved in the development of HF in humans. Methods and Results: Nine HF patients (NYHA II or III, LV ejection fraction 26.3±3.0%) and 8 healthy controls were studied. The mean age and male gender were comparable between HF and controls (51.2±5.1 vs. 45.1±4.5 years and 77.8 vs. 75.0%). The causes of HF were idiopathic dilated cardiomyopathy in 3, ischemic in 2, and others in 4 patients. Plasma BNP was significantly higher in HF than in controls (739.4±207.2 vs. 19.8±6.5 pg/mL, P <0.01). The number of circulating iNKT cells, identified by the positive-staining of Vα24-Jα18 T Cell Receptor by flow-cytometric analysis, was significantly lower in HF (747±85 vs. 1058±271 counts/mL, P <0.01). Its ratio to the total lymphocyte was also significantly lower (0.111±0.004 vs. 0.146±0.035%, P <0.01). Plasma interleukin-6 and high-sensitivity CRP were significantly higher in HF (3.99±0.86 vs. 0.78±0.14 pg/mL and 0.28±0.10 vs. 0.06±0.02 mg/dL, respectively, both P <0.01). LV ejection fraction ( r =0.72, P <0.05) and plasma log BNP ( r =-0.70, P <0.05) were significantly correlated to the ratio of iNKT cells among HF patients. Conclusions: Circulating iNKT cells were decreased in HF patients, suggesting that they have a potential role in the development of human HF.