CD1d-mediated Recognition of an α-Galactosylceramide by Natural Killer T Cells Is Highly Conserved through Mammalian Evolution

Brossay, Laurent; Chioda, Mariacristina; Burdin, Nicolas; Koezuka, Yasuhiko; Casorati, Giulia; Kronenberg, Mitchell

doi:10.1084/jem.188.8.1521

Cited by 609 publications

(486 citation statements)

References 45 publications

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“…First, the flow cytometry analysis of T cell hybridomas with the multimers was highly consistent with the functional assays of these cells. Concordant IL-2 release and binding results were obtained for reactivity to mCD1d in the absence of α-GalCer, for the α-GalCer requirement for different CD1d restricted T cells, and for the analysis of cross-reactivity with hCD1d 16 21 22. Second, the distribution and phenotype of tetramer-binding cells agrees with previous phenotypic analyses of CD1d-dependent NK T lymphocytes.…”

Section: Discussionsupporting

confidence: 84%

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

Matsuda

Naidenko

Gapin

et al. 2000

The Journal of Experimental Medicine

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804

823

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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.

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Section: Discussionsupporting

confidence: 84%

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

Matsuda

Naidenko

Gapin

et al. 2000

The Journal of Experimental Medicine

Self Cite

804

823

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“…The glycolipid antigen a-GalCer is presented to NKT cells via the MHC class I-like molecule CD1d expressed on APC [9,10]. Because CpG ODN enhance a-GalCermediated stimulation, we asked whether PDC express CD1d and thus are able to present a-GalCer to NKT cells.…”

Section: Identification Of MDC As the Main Apc For Nkt Cells Within Hmentioning

confidence: 99%

“…tially accumulate in the liver though with a far lower frequency than in mice (4% of hepatic T cells) ([6, 7] and reviewed in [1,5]). Due to the conserved TCR, both mouse and human NKT cells recognise the same specific glycolipid antigen a-galactosylceramide (a-GalCer) when presented by CD1d molecules on antigen-presenting cells (APC) [8][9][10]. Originally isolated from a marine sponge, aGalCer was first described as an agent with strong antimetastatic activity in mice and later found to specifically activate NKT cells in a CD1d-restricted manner [8,11,12].…”

Section: Introductionmentioning

confidence: 99%

CpG ODN enhance antigen-specific NKT cell activation via plasmacytoid dendritic cells

et al. 2005

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Human Va24 + Vb11 + natural killer T cells (NKT cells) are "natural memory" T cells that detect glycolipid antigens such as a-galactosylceramide (a-GalCer) presented on CD1d.In the present study we found that highly purified Va24 + NKT cells lack TLR9 mRNA, and thus are not sensitive towards stimulation with CpG oligodeoxynucleotides (ODN). Within PBMC, however, CpG ODN synergistically activated NKT cells stimulated with their cognate antigen a-GalCer. Depletion of plasmacytoid dendritic cells (PDC) or myeloid dendritic cells (MDC) revealed that both DC subsets were necessary for the synergistic activation of NKT cells by a-GalCer and CpG ODN. While PDC were responsible for the stimulation of NKT cells with CpG ODN, MDC but not PDC presented a-GalCer via CD1d. Partial activation of NKT cells was mediated by PDC-derived IFN-a, whereas full activation of NKT cells as indicated by IFN-c production required cell-tocell contact of PDC and NKT cells in addition to IFN-a; OX40 was involved in this interaction. We conclude that CpG-activated PDC enhance a-GalCer-specific NKT cell activation, and bias activated NKT cells towards a Th1 phenotype. Our results lead to a novel concept of PDC function: to regulate effector activity of antigen-stimulated T cells in a cell contact-dependent manner without the need of simultaneous presentation of the cognate T cell antigen. IntroductionNatural killer T (NKT) cells represent a small subset of non-conventional innate T cells with a restricted TCR repertoire for the recognition of glycolipid antigens presented on CD1d, an MHC class I-like molecule. NKT cells express markers of NK cells and exhibit an activated memory phenotype. Depending on the microenvironment and the type of stimulation, they can release large amounts of both Th1 and Th2 cytokines (especially IL-4 and IFN-c) and show cytotoxic activity in vitro (reviewed in [1][2][3]). In both mice and man NKT cells express a homologous semi-invariant TCR that in humans consists of a Va24 chain preferentially paired with a Vb11 chain [4]. In mice, NKT cells are most frequent in the liver (about 30% of hepatic T cells), bone marrow and thymus (reviewed in [5]). Smaller NKT cell populations are present in spleen and blood (reviewed in [5]). Similar to their murine counterparts, human NKT cells preferen-A. M., S. R. and V. H. equally contributed to this manuscript. tially accumulate in the liver though with a far lower frequency than in mice (4% of hepatic T cells) ([6, 7] and reviewed in [1,5]). Due to the conserved TCR, both mouse and human NKT cells recognise the same specific glycolipid antigen a-galactosylceramide (a-GalCer) when presented by CD1d molecules on antigen-presenting cells (APC) [8][9][10]. Originally isolated from a marine sponge, aGalCer was first described as an agent with strong antimetastatic activity in mice and later found to specifically activate NKT cells in a CD1d-restricted manner [8,11,12]. Glycolipid antigens similar to a-GalCer have been detected in certain bacteria and under some abnormal conditions...

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“…4 The CD1d molecule has been well conserved throughout mammalian evolution and lacks allelic polymorphism. [5][6][7] After activation, V␣14 NKT cells inhibit tumor metastasis in certain experimental animal models. 8 -10 Furthermore, i.v.…”

mentioning

confidence: 99%

Preserved IFN‐α production of circulating Vα24 NKT cells in primary lung cancer patients

Motohashi

Kobayashi

Ito

et al. 2002

Intl Journal of Cancer

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Human V␣24 NKT cells bearing an invariant V␣24J␣Q antigen receptor, the counterpart of murine V␣14 NKT cells, are activated by a specific ligand, ␣-GalCer, in a CD1d-dependent manner. Here, we demonstrate decreased numbers of circulating V␣24 NKT cells in patients with primary lung cancer compared to healthy volunteers. However, V␣24 NKT cells and DCs from lung cancer patients were functionally normal, even in the presence of tumor. Furthermore, levels of V␣24 NKT cells in surgically resected lung tissue appeared to be equivalent to those of V␣14 NKT cells in the mouse lung. Levels of V␣24 NKT cells in the tumor tissue itself were increased about 2.5 times. Administration of ␣-GalCer-pulsed DCs expanded V␣14 NKT cells in the lung more than 10 times, and the increased levels were sustained for 1 week. This may explain the previous finding that ␣-GalCer-pulsed DCs exerted strong antitumor activity in mouse lung tumor metastatic models. The potential use of ␣-GalCer-pulsed DCs for immunotherapy aimed at activating endogenous V␣24 NKT cells in the lung of cancer patients is discussed. © 2002 Wiley-Liss, Inc. Key words: V␣24 NKT cell; IFN-␥ primary lung cancer; ␣-galactosylceramide; single-cell sorting RT-PCRMurine V␣14 NKT cells are characterized by coexpression of NK1.1, an NK cell marker, and an invariant antigen receptor encoded by V␣14 and J␣281 gene segments. 1-3 V␣14 NKT cells recognize a glycolipid, ␣-GalCer, in a CD1d-depenent fashion. 4 The CD1d molecule has been well conserved throughout mammalian evolution and lacks allelic polymorphism. 5-7 After activation, V␣14 NKT cells inhibit tumor metastasis in certain experimental animal models. 8 -10 Furthermore, i.v. injection of ␣-GalCer-pulsed DCs expressed a potent antitumor effect in a B16 melanoma liver metastasis model, where metastasized tumor nodules were eradicated. 11 Human NKT cells bearing the invariant V␣24J␣Q receptor are considered to be the counterpart of murine V␣14 NKT cells and may recognize antigens similar to those of murine V␣14 NKT cells because of striking homology between human V␣24 and mouse V␣14 receptors, particularly in their complementarity-determining region 3. 2 Indeed, human V␣24 NKT cells were activated by ␣-GalCer in a CD1d-dependent fashion 5,12,13 and showed strong antitumor activity upon ␣-GalCer stimulation. 14,15 Human V␣24 NKT cells play crucial roles in various immune responses, including antitumor and autoimmune responses. 16 -19 These reports demonstrated selective reduction in V␣24 NKT cell numbers. Little is known, however, about the nature of V␣24 NKT cells in primary lung cancer patients.We investigated the function of V␣24 NKT cells in peripheral blood and lung of patients with lung cancer. The numbers of V␣24 NKT cells were reduced, whereas the function of freshly isolated V␣24 NKT cells appeared to be preserved in tumor-bearing patients. Furthermore, the ability to present ␣-GalCer by patient DCs was within a normal range. Administration of ␣-GalCer-pulsed DCs expanded V␣14 NKT cells in the lung more than 10 ti...

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CD1d-mediated Recognition of an α-Galactosylceramide by Natural Killer T Cells Is Highly Conserved through Mammalian Evolution

Cited by 609 publications

References 45 publications

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

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

CpG ODN enhance antigen-specific NKT cell activation via plasmacytoid dendritic cells

Preserved IFN‐α production of circulating Vα24 NKT cells in primary lung cancer patients

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