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* Department of Pathology and Immunology, Monash University, Central and Eastern Clinical School, Prahran, Victoria, Australia;
Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121; and
Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, East Melbourne, Victoria, Australia
NKT cells are enigmatic lymphocytes that respond to glycolipid Ags presented by CD1d. Although they are key immunoregulatory cells, with a critical role in immunity to cancer, infection, and autoimmune diseases, little is known about how they respond to antigenic challenge. Current theories suggest that NKT cells die within hours of stimulation, implying that their direct impact on the immune system derives from the initial cytokine burst released before their death. Here we show that NKT cell disappearance results from TCR down-regulation rather than apoptosis, and that they expand to many times their normal number in peripheral tissues within 2–3 days of stimulation, before contracting to normal numbers over subsequent days. This expansion is associated with ongoing cytokine production, biased toward a Th1 (IFN-
+ IL-4-) phenotype, in contrast to their initial Th0 (IFN-+IL-4+) phenotype. This study provides critical new insight into how NKT cells can have such a major impact on immune responses, lasting many days beyond the initial stimulation of these cells.
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T. Saito, A. Okumura, H. Watanabe, M. Asano, A. Ishida-Okawara, J. Sakagami, K. Sudo, Y. Hatano-Yokoe, J. S. Bezbradica, S. Joyce, et al. Increase in Hepatic NKT Cells in Leukocyte Cell-Derived Chemotaxin 2-Deficient Mice Contributes to Severe Concanavalin A-Induced Hepatitis J. Immunol., July 1, 2004; 173(1): 579 - 585. [Abstract] [Full Text] [PDF]
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R. Nakagawa, T. Inui, I. Nagafune, Y. Tazunoki, K. Motoki, A. Yamauchi, M. Hirashima, Y. Habu, H. Nakashima, and S. Seki Essential Role of Bystander Cytotoxic CD122+CD8+ T Cells for the Antitumor Immunity Induced in the Liver of Mice by {alpha}-Galactosylceramide J. Immunol., June 1, 2004; 172(11): 6550 - 6557. [Abstract] [Full Text] [PDF]
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S. E.A. Street, Y. Hayakawa, Y. Zhan, A. M. Lew, D. MacGregor, A. M. Jamieson, A. Diefenbach, H. Yagita, D. I. Godfrey, and M. J. Smyth Innate Immune Surveillance of Spontaneous B Cell Lymphomas by Natural Killer Cells and {gamma}{delta} T Cells J. Exp. Med., March 15, 2004; 199(6): 879 - 884. [Abstract] [Full Text] [PDF]
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K. A. Muhlen, J. Schumann, F. Wittke, S. Stenger, N. van Rooijen, L. van Kaer, and G. Tiegs NK Cells, but Not NKT Cells, Are Involved in Pseudomonas aeruginosa Exotoxin A-Induced Hepatotoxicity in Mice J. Immunol., March 1, 2004; 172(5): 3034 - 3041. [Abstract] [Full Text] [PDF]
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J. R. Ortaldo, H. A. Young, R. T. Winkler-Pickett, E. W. Bere Jr., W. J. Murphy, and R. H. Wiltrout Dissociation of NKT Stimulation, Cytokine Induction, and NK Activation In Vivo by the Use of Distinct TCR-Binding Ceramides J. Immunol., January 15, 2004; 172(2): 943 - 953. [Abstract] [Full Text] [PDF]
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M. Nieda, M. Okai, A. Tazbirkova, H. Lin, A. Yamaura, K. Ide, R. Abraham, T. Juji, D. J. Macfarlane, and A. J. Nicol Therapeutic activation of V{alpha}24+V{beta}11+ NKT cells in human subjects results in highly coordinated secondary activation of acquired and innate immunity Blood, January 15, 2004; 103(2): 383 - 389. [Abstract] [Full Text] [PDF]
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