Tracking the Response of Natural Killer T Cells to a Glycolipid Antigen Using Cd1d Tetramers

By J. Matsuda, O. Naidenko, L. Gapin, T. Nakayama, Masaru Taniguchi, Chyung-Ru Wang, Y. Koezuka, M. Kronenberg. Journal of Experimental Medicine, 2000

999 citations recorded by the source corpus.

A major group of natural killer (NK) T cells express an invariant Vα14+ T cell receptor (TCR) specific for the lipoglycan α-galactosylceramide (α-GalCer), which is presented by CD1d. These cells may have an important immune regulatory function, but an understanding of their biology has been hampered by the lack of suitable reagents for tracking them in vivo. Here we show that tetramers of mouse CD1d loaded with α-GalCer are a sensitive and highly specific reagent for identifying Vα14+ NK T cells. Using these tetramers, we find that α-GalCer–specific T lymphocytes are more widely distributed than was previously appreciated, with populations of largely NK1.1− but tetramer-binding T cells present in the lymph nodes and the intestine. Injection of α-GalCer leads to the production of both interferon γ and interleukin 4 by nearly all NK T cells in the liver and the majority of the spleen within 2 h. These cells mostly disappear by 5 h, and they do not reappear after 1 wk. Curiously, tetramer-positive thymocytes do not rapidly synthesize cytokines, nor do they undergo decreases in cell number after lipid antigen stimulation, although they express equivalent TCR levels. In summary, the data presented here demonstrate that α-GalCer–specific NK T cells undergo a unique and highly compartmentalized response to antigenic stimulation.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/62e58357a8fbf5dd13375b03ae4d3635e0caf685

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Citations in the corpus

Natural killer T cells recognize diacylglycerol antigens from pathogenic bacteria (2006, methodology): “We evaluated V α 14 i NKT cell activation by measuring CD25 and CD69 on the surface of V α 14 i NKT cells, which bind to CD1d tetramers loaded with α-GalCe”
The Vα14 NKT Cell TCR Exhibits High-Affinity Binding to a Glycolipid/CD1d Complex1 (2002, methodology): “It is noteworthy that the NKT cell TCR affinity for -GalCer-loaded CD1d molecules is higher that the affinity of any other published experimental Ags for CD4 and CD8 T cells (29, 30).”
The Linkage of Innate to Adaptive Immunity via Maturing Dendritic Cells In Vivo Requires CD40 Ligation in Addition to Antigen Presentation and CD80/86 Costimulation (2004, background): “Also, it is known that IFN- –producing NKT cells are evident at 2 h, but not 5 h, after -GalCer (34).”
Hepatic T cells and liver tolerance (2003, methodology): “Another tool to study the function of NKT cells is α-galactosyl ceramide (α-GalCer), a molecule derived from marine sponges that causes acute NKT-cell activation, resulting in the synthesis of IFN-γ and IL-4, followed by deletion of the cell”
T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse (2011, methodology): “Enrichment of CD1d+ cells was performed using an adult thymus as previously described (Matsuda et al., 2000).”
Vα24-JαQ-Independent, CD1d-Restricted Recognition of α-Galactosylceramide by Human CD4+ and CD8αβ+ T Lymphocytes1 (2002, methodology): “We and others have recently described the use of rCD1dtetramers loaded with GC for sensitive and specific identification of both murine invariant V 14-J 281 or human V 24 V 11 NKT cells (17, 21, 22).”
The crystal structure of human CD1d with and without α-galactosylceramide (2005, background): “The glycolipid α-galactosylceramide (α-GalCer), isolated from a marine sponge, binds human CD1d and mouse CD1d with high affinity and specifically activates the main population of CD1d-restricted T cells called NKT cell”
Constitutive Cytokine mRNAs Mark Natural Killer (NK) and NK T Cells Poised for Rapid Effector Function (2003, methodology): “Activation of NK T cells by systemically administered anti-CD3 causes a burst of both IL-4 and IFN- detected in tissues and serum that is lost in the absence of these cells (15, 22).”