The cytokine profile of human NKT cells and PBMCs is dependent on donor sex and stimulus

Med Microbiol Immunol. 2016 Aug;205(4):321-32. doi: 10.1007/s00430-016-0449-y. Epub 2016 Feb 20.


Sex-related variations in natural killer T (NKT) cells may influence immunoregulation and outcome of infectious and autoimmune diseases. We analyzed sex-specific differences in peripheral blood NKTs and peripheral blood mononuclear cells (PBMCs) from men and women and determined the frequencies of NKT cells and their subpopulations [CD4(+); CD8(+); double negative (DN)] and the levels of cytokine production following stimulation with the NKT cell ligands α-Galactosylceramide (αGalCer) and Entamoeba histolytica lipopeptidephosphoglycan (Lotter et al. in PLoS Pathog 5(5):e1000434, 2009). Total and DN NKT cells were more abundant in women than in men. In women, αGalCer induced higher production of intracellular IFNγ, IL-4, IL-17 and TNF by CD4(+) and DN(+)NKT cells. Both ligands induced expression of multiple cytokines in PBMCs and influenced the ratio of NKT cell subpopulations during long-term culture. Although the sex-specific differences in frequencies of NKT cells and their subpopulations were marginal, the significant sex-specific differences in cytokine production might influence disease outcomes.

Keywords: Cytokines; Entamoeba histolytica; Glycolipid; Human; Immune response; NKT cells; Sex difference; αGalCer.

MeSH terms

  • Adult
  • Blood Donors
  • Cytokines / metabolism*
  • Female
  • Galactosylceramides / metabolism
  • Humans
  • Immunologic Factors / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Middle Aged
  • Natural Killer T-Cells / drug effects
  • Natural Killer T-Cells / metabolism*
  • Peptidoglycan / metabolism
  • Phospholipids / metabolism
  • Sex Factors


  • Cytokines
  • Galactosylceramides
  • Immunologic Factors
  • Peptidoglycan
  • Phospholipids
  • alpha-galactosylceramide
  • lipopeptidophosphoglycan