title: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Björkbacka
authors.affiliation: Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: K E
authors.initials: KE
authors.lastname: Berg
authors.affiliation: Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Manjer
authors.affiliation: Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: D
authors.initials: D
authors.lastname: Engelbertsen
authors.affiliation: Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Wigren
authors.affiliation: Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Ljungcrantz
authors.affiliation: Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Andersson
authors.affiliation: Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Hedblad
authors.affiliation: Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: G N
authors.initials: GN
authors.lastname: Fredrikson
authors.affiliation: Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Nilsson
mesh_terms: D000368:Aged; D017252:CD3 Complex / Q000097:blood; D015704:CD4 Antigens / Q000097:blood*; D019002:CD56 Antigen / Q000097:blood*; D003327:Coronary Disease / Q000097:blood*; D016207:Cytokines / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D008297:Male; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D011446:Prospective Studies
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens; D019002:CD56 Antigen; D016207:Cytokines; C522918:NCAM1 protein, human; D010446:Peptide Fragments; C069261:interferon gamma (1-39); D007371:Interferon-gamma
keywords: NKT-like cells; cancer; cardiovascular disease