Superior Protection against Malaria and Melanoma Metastases by a C-glycoside Analogue of the Natural Killer T Cell Ligand α-Galactosylceramide

Schmieg, John; Yang, Guangli; Franck, Richard W.; Tsuji, Moriya

doi:10.1084/jem.20031192

Cited by 369 publications

(389 citation statements)

References 31 publications

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“…The cytokine profile of NKT cells is possibly influenced by the quality of the TCR signal, which is dependent on different antigens. An -Galcer analogue with a shortened sphingosine stimulates a higher ratio of IL-4 to IFN- secretion, while a C-glycoside analogue of -Galcer promotes a higher ratio of IFN- to IL-4 (7,8). However, there is no structural basis for predicting how a compound will affect the cytokine profile produced by activated NKT cells.…”

Section: Introductionmentioning

confidence: 99%

EBV-Induced Human CD8+ NKT Cells Synergise CD4+ NKT Cells Suppressing EBV-Associated Tumours Upon Induction of Th1-Bias

Xiao

Zhou

et al. 2009

Cell Mol Immunol

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Section: Introductionmentioning

confidence: 99%

EBV-Induced Human CD8+ NKT Cells Synergise CD4+ NKT Cells Suppressing EBV-Associated Tumours Upon Induction of Th1-Bias

Xiao

Zhou

et al. 2009

Cell Mol Immunol

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“…Crosstalk between the two cell types involves CD40/CD40L interactions but does not The adjuvant effects of iNKT cells, together with their cytotoxic activities and capacity to secrete diverse cytokines, and the ease by which these cells can be expanded using conserved antigens have placed these cells as important immunomodulators in the tissues and potential targets for immunotherapy. Therapeutic activation of iNKT cells in murine models can prevent tumor growth [182][183][184], ameliorate autoimmune [185,186] and metabolic [187] disease, and protect against microbial infection [188]. Numerical and functional iNKT cell deficiencies have been reported in a number of human diseases [189][190][191][192].…”

Section: Priming Of Cd4 + and Cd8 + T Cells By Vc9/vd2 T Cells: A Newmentioning

confidence: 99%

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

Tyler

Doherty

Moser

et al. 2015

Cellular Immunology

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a b s t r a c tUnconventional T cells are gaining center stage as important effector and regulatory cells that orchestrate innate and adaptive immune responses. Human Vc9/Vd2 T cells are amongst the best understood unconventional T cells, as they are easily accessible in peripheral blood, can readily be expanded and manipulated in vitro, respond to microbial infections in vivo and can be exploited for novel tumor immunotherapies. We here review findings that suggest that Vc9/Vd2 T cells, and possibly other unconventional human T cells, play an important role in bridging innate and adaptive immunity by promoting the activation and differentiation of various types of antigen-presenting cells (APCs) and even turning into APCs themselves, and thereby pave the way for antigen-specific effector responses and long-term immunological memory. Although the direct physiological relevance for most of these mechanisms still needs to be demonstrated in vivo, these findings may have implications for novel therapies, diagnostic tests and vaccines.Ó 2015 Published by Elsevier Inc. Introduction cd T cells represent a third lineage of lymphocytes expressingre-arranged antigen receptors that co-evolved with 'classical' B cells and ab T cells over 400 million years, arguing for a crucial and non-redundant contribution of each lymphocyte to effective immune responses, and hence the evolutionary survival of all jawed vertebrate species [1]. 30 years have passed since the accidental and unexpected cloning of the cd T cell receptor (TCR) and the subsequent realization that ab T cells and cd T cells are fundamentally different with respect to the types of antigens they recognize and the distinct effector functions triggered upon such recognition. However, the manifold contributions of cd T cells to homeostasis, inflammation, infection and tumor surveillance have historically been neglected and are only beginning to be integrated into comprehensive models of the immune system [1][2][3][4][5][6][7].1. Innate-like pattern recognition by human Vc9/Vd2 T cells Like other 'unconventional' T cells carrying an ab TCR such as mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells, cd T cells are characterized by a markedly restrictedTCR usage that allows them to recognize self and non-self molecules in the absence of classical antigen presentation via MHC I or MHC II. Vc9/Vd2 + cd T cells represent the major cd T cell subset in human peripheral blood where they typically comprise 1-5% in healthy adults [8]. In many microbial infections, Vc9/Vd2 T cells increase locally and/or systemically [9,10] and can reach in excess of 50% of all peripheral T cells within a matter of days [11], revealing a fundamental role of this unconventional T cell population in acute disease and suggesting their exploitation for diagnostic and therapeutic purposes [12][13][14]. Vc9/Vd2 T cells uniformly respond to a class of low molecular weight molecules often referred to as 'phosphoantigens' that represent metabolites of the isoprenoid biosynthesis...

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“…For example, several synthetic agonist analogs of α-Galcer have distinct effects on iNKT cell function. The OCH [97] and C20:2 [98] analogs have both been shown to elicit a predominantly Th2-like response while α-C-Galcer drives a Th1 response [99]. The reason why these analogs induce different functional responses following iNKT cell stimulation is unclear.…”

Section: The Type Of Inkt Cell Stimulationmentioning

confidence: 99%

CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system

Matsuda

Mallevaey

Scott‐Browne

et al. 2008

Current Opinion in Immunology

346

393

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SummaryNatural Killer T cells are a distinct lymphocyte lineage that regulates a broad range of immune responses. NKT cells recognize glycolipids presented by the non-classical MHC molecule CD1d. Structural insight into the TCR/glycolipid/CD1d tri-complex has revealed an unusual and unexpected mode of recognition. Recent studies have also identified some of the signaling events during NKT cell development that give NKT cells their innate phenotype. Pathogen-derived glycolipid antigens continue to be found, and new mechanisms of NKT cell activation have been described. Finally, NKT cells have been shown to be remarkably versatile in function during various immune responses. Whether these extensive functional capacities can be attributed to a single population sensitive to environmental cues or if functionally distinct NKT cell subpopulations exist remains unresolved.

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Superior Protection against Malaria and Melanoma Metastases by a C-glycoside Analogue of the Natural Killer T Cell Ligand α-Galactosylceramide

Cited by 369 publications

References 31 publications

EBV-Induced Human CD8+ NKT Cells Synergise CD4+ NKT Cells Suppressing EBV-Associated Tumours Upon Induction of Th1-Bias

EBV-Induced Human CD8+ NKT Cells Synergise CD4+ NKT Cells Suppressing EBV-Associated Tumours Upon Induction of Th1-Bias

Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system

CD1d-restricted iNKT cells, the ‘Swiss-Army knife’ of the immune system

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