Cutting Edge: Activation by Innate Cytokines or Microbial Antigens Can Cause Arrest of Natural Killer T Cell Patrolling of Liver Sinusoids

Abstract Natural killer T (NKT) cells are innate-like lymphocytes that rapidly secrete large amounts of effector cytokines upon activation. Recognition of α-linked glycolipids presented by CD1d leads to the production of IL-4, IFN-γ, or both, while direct activation by the synergistic action of IL-12 and IL-18 leads to IFN-γ production only. We previously reported that in vitro cultured dendritic cells can modulate NKT cell activation and, using intravital fluorescence laser scanning microscopy, we reported that the potent stimulation of NKT cells results in arrest within hepatic sinusoids. In this study, we examine the relationship between murine NKT cell patrolling and activation. We report that NKT cell arrest results from activation driven by limiting doses of a bacteria-derived weak agonist, galacturonic acid-containing glycosphingolipid, or a synthetic agonist, α-galactosyl ceramide. Interestingly, NKT cell arrest also results from IL-12 and IL-18 synergistic activation. Thus, innate cytokines and natural microbial TCR agonists trigger sinusoidal NKT cell arrest and an effector response.