CD4+CD56+ natural killer T-like cells secreting interferon-γ are associated with incident coronary events

Abstract

Background: CD3+CD56+ natural killer T (NKT)-like cells are a subset of T cells characterized by expression of NK receptors and potent antitumour activity. It has also been suggested that they have a role in autoimmune disease, and levels of NKT-like cells are elevated in patients with coronary disease. Objectives: To investigate whether high levels of CD3+CD56+ NKT-like cells are associated with an increased incidence of cardiovascular disease and a lower incidence of cancer. Methods: This was a prospective study including 700 subjects participating in the baseline investigation of the Malmö Diet and Cancer study between 1991 and 1994. Leucocytes obtained at the baseline investigation and stored at -140 °C were thawed and CD3+CD56+ cells analysed by flow cytometry. The incidence rates of cancer and coronary events during a mean follow-up of 15 years were determined through national registers. Results: Subjects in the lowest tertile of interferon (IFN)-γ-expressing CD4+CD56+ cells were found to have an increased risk of incidence of coronary events (log-rank test: P < 0.05). This association remained significant after controlling for age, sex, smoking, body mass index, hypertension, diabetes and the Th1/Th2 and Th1/Treg cell ratios in a Cox proportional hazards regression model (hazard ratio 1.98, 95% confidence interval 1.24-3.16), but not when the LDL/HDL ratio was included in the model. There were no associations between CD3+CD56+ NKT-like cells and incident cancer. Conclusions: The present results could not confirm the hypothesis that low levels of CD3+CD56+ NKT-like cells are associated with a higher incidence of cancer and a lower incidence of cardiovascular disease. However, we found that low levels of IFN-γ-expressing CD3+CD4+CD56+ NKT-like cells were associated with an increased incidence of coronary events and that this association may be dependent on lipoproteins.