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Cutting Edge: Activation by Innate Cytokines or Microbial Antigens Can Cause Arrest of Natural Killer T Cell Patrolling of Liver Sinusoids¹

Peter Velázquez^*, Thomas O. Cameron^*, Yuki Kinjo, Niranjana Nagarajan, Mitchell Kronenberg and Michael L. Dustin^2,*

^* Molecular Pathogenesis Program, The Helen L. and Martin S. Kimmel Center for Biology and Medicine at Skirball Institute of Biomolecular Medicine, New York, NY 10016; La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; and Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720

Natural killer T (NKT) cells are innate-like lymphocytes that rapidly secrete large amounts of effector cytokines upon activation. Recognition of -linked glycolipids presented by CD1d leads to the production of IL-4, IFN-, or both, while direct activation by the synergistic action of IL-12 and IL-18 leads to IFN- 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, -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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institute of Allergy and Infectious Diseases, National Institutes of Health Grants R01 AI055037-03 (to M.L.D.) and R37 AI 71922 (to M.K.), grants from the Irene Diamond Fund (to M.L.D.) and the Cancer Research Institute (to Y.K.), and National Institute of Diabetes and Digestive and Kidney Disease Grant F32-DK078153 (to P.V.).

² Address correspondence and reprint requests to Dr. Michael L. Dustin, Molecular Pathogenesis Program, The Helen L. and Martin S. Kimmel Center for Biology and Medicine at Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016. E-mail address: dustin{at}saturn.med.nyu.edu

³ Abbreviations used in this paper: NKT, natural killer T; GalA-GSL, galacturonic acid-containing glycosphingolipid; GalCer, -galactosyl ceramide; EGFP, enhanced green fluorescent protein.

⁴ The online version of this article contains supplemental material.