title: 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 alpha-linked glycolipids presented by CD1d leads to the production of IL-4, IFN-gamma, or both, while direct activation by the synergistic action of IL-12 and IL-18 leads to IFN-gamma 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, alpha-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.
authors.affiliation: Molecular Pathogenesis Program, The Helen L. and Martin S. Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, New York, NY 10016, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Velázquez
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Cameron
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kinjo
authors.forename: Niranjana
authors.initials: N
authors.lastname: Nagarajan
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kronenberg
authors.forename: Michael L
authors.initials: ML
authors.lastname: Dustin
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000502:physiology*; D002464:Cell Migration Inhibition / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D016207:Cytokines / Q000502:physiology*; D005699:Galactosylceramides / Q000008:administration & dosage / Q000032:analysis; D006603:Hexuronic Acids / Q000008:administration & dosage / Q000032:analysis; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D005699:Galactosylceramides; D006603:Hexuronic Acids; C007819:galacturonic acid