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

1998 ◽  
Vol 188 (8) ◽  
pp. 1521-1528 ◽  
Author(s):  
Laurent Brossay ◽  
Mariacristina Chioda ◽  
Nicolas Burdin ◽  
Yasuhiko Koezuka ◽  
Giulia Casorati ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Natural Killer ◽  
Human Peripheral Blood ◽  
Cell Subset ◽  
Cell Receptor ◽  
Recognition System ◽  
Human T Cells ◽  
Nk T Cells ◽  
Killer T Cells

Natural killer (NK) T cells are a lymphocyte subset with a distinct surface phenotype, an invariant T cell receptor (TCR), and reactivity to CD1. Here we show that mouse NK T cells can recognize human CD1d as well as mouse CD1, and human NK T cells also recognize both CD1 homologues. The unprecedented degree of conservation of this T cell recognition system suggests that it is fundamentally important. Mouse or human CD1 molecules can present the glycolipid α-galactosylceramide (α-GalCer) to NK T cells from either species. Human T cells, preselected for invariant Vα24 TCR expression, uniformly recognize α-GalCer presented by either human CD1d or mouse CD1. In addition, culture of human peripheral blood cells with α-GalCer led to the dramatic expansion of NK T cells with an invariant (Vα24+) TCR and the release of large amounts of cytokines. Because invariant Vα14+ and Vα24+ NK T cells have been implicated both in the control of autoimmune disease and the response to tumors, our data suggest that α-GalCer could be a useful agent for modulating human immune responses by activation of the highly conserved NK T cell subset.

scholarly journals CD1d-restricted Recognition of Synthetic Glycolipid Antigens by Human Natural Killer T Cells

1998 ◽  
Vol 188 (8) ◽  
pp. 1529-1534 ◽  
Author(s):  
Franca M. Spada ◽  
Yasuhiko Koezuka ◽  
Steven A. Porcelli
Keyword(s):  
T Cells ◽  
T Cell ◽  
Natural Killer ◽  
Cell Subset ◽  
Cell Receptor ◽  
Immune Recognition ◽  
Cell Clones ◽  
Nk T Cells ◽  
Circulating T Cells ◽  
Antigen Presenting

A conserved subset of mature circulating T cells in humans expresses an invariant Vα24-JαQ T cell receptor (TCR)-α chain rearrangement and several natural killer (NK) locus–encoded C-type lectins. These human T cells appear to be precise homologues of the subset of NK1.1+ TCR-α/β+ T cells, often referred to as NK T cells, which was initially identified in mice. Here we show that human NK T cell clones are strongly and specifically activated by the same synthetic glycolipid antigens as have been shown recently to stimulate murine NK T cells. Responses of human NK T cells to these synthetic glycolipids, consisting of certain α-anomeric sugars conjugated to an acylated phytosphingosine base, required presentation by antigen-presenting cells expressing the major histocompatibility complex class I–like CD1d protein. Presentation of synthetic glycolipid antigens to human NK T cells required internalization of the glycolipids by the antigen-presenting cell and normal endosomal targeting of CD1d. Recognition of these compounds by human NK T cells triggered proliferation, cytokine release, and cytotoxic activity. These results demonstrate a striking parallel in the specificity of NK T cells in humans and mice, thus providing further insight into the potential mechanisms of immune recognition by NK T cells and the immunological function of this unique T cell subset.

scholarly journals A Critical Role for Natural Killer T Cells in Immunosurveillance of Methylcholanthrene-induced Sarcomas

2002 ◽  
Vol 196 (1) ◽  
pp. 119-127 ◽  
Author(s):  
Nadine Y. Crowe ◽  
Mark J. Smyth ◽  
Dale I. Godfrey
Keyword(s):  
T Cells ◽  
T Cell ◽  
Natural Killer ◽  
Critical Role ◽  
Physiological Role ◽  
Cell Receptor ◽  
Interferon Γ ◽  
Tumor Rejection ◽  
Nk T Cells ◽  
Nk T Cell

Natural killer (NK) T cells initiate potent antitumor responses when stimulated by exogenous factors such as interleukin (IL)-12 or α-galactosylceramide (α-GalCer), however, it is not clear whether this reflects a physiological role for these cells in tumor immunity. Through adoptive transfer of NK T cells from wild-type to NK T cell–deficient (T cell receptor [TCR] Jα281−/−) mice, we demonstrate a critical role for NK T cells in immunosurveillance of methylcholanthrene (MCA)-induced fibrosarcomas, in the absence of exogenous stimulatory factors. Using the same approach with gene-targeted and/or antibody-depleted donor or recipient mice, we have shown that this effect depends on CD1d recognition and requires the additional involvement of both NK and CD8+ T cells. Interferon-γ production by both NK T cells and downstream, non-NK T cells, is essential for protection, and perforin production by effector cells, but not NK T cells, is also critical. The protective mechanisms in this more physiologically relevant system are distinct from those associated with α-GalCer–induced, NK T cell–mediated, tumor rejection. This study demonstrates that, in addition to their importance in tumor immunotherapy induced by IL-12 or α-GalCer, NK T cells can play a critical role in tumor immunosurveillance, at least against MCA-induced sarcomas, in the absence of exogenous stimulation.

scholarly journals Repertoire Development and the Control of Cytotoxic/Effector Function in HumanγδT Cells

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Elizabeth M. Urban ◽  
Andrei I. Chapoval ◽  
C. David Pauza
Keyword(s):  
T Cells ◽  
T Cell ◽  
Human Peripheral Blood ◽  
Cell Subset ◽  
Cell Receptor ◽  
Effector Function ◽  
Repertoire Selection ◽  
Cd56 Expression ◽  
Lineage Markers ◽  
Cytotoxic Effector

T cells develop into two major populations distinguished by their T cell receptor (TCR) chains. Cells with theαβTCR generally express CD4 or CD8 lineage markers and mostly fall into helper or cytotoxic/effector subsets. Cells expressing the alternateγδTCR in humans generally do not express lineage markers, do not require MHC for antigen presentation, and recognize nonpeptidic antigens. We are interested in the dominant Vγ2Vδ2+ T cell subset in human peripheral blood and the control of effector function in this population. We review the literature onγδT cell generation and repertoire selection, along with recent work on CD56 expression and defining a cytotoxic/effector lineage within the phosphoantigen-reactive Vγ2Vδ2 cells. A unique mechanism for MHC-independent repertoire selection is linked to the control of effector function that is vital to the role forγδT cells in tumor surveillance. Better understanding of these mechanisms will improve our ability to exploit this population for tumor immunotherapy.

scholarly journals Generation of Novel Traj18-Deficient Mice Lacking Vα14 Natural Killer T Cells with an Undisturbed T Cell Receptor α-Chain Repertoire

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0153347 ◽  
Author(s):  
Nyambayar Dashtsoodol ◽  
Tomokuni Shigeura ◽  
Ritsuko Ozawa ◽  
Michishige Harada ◽  
Satoshi Kojo ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Natural Killer ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Natural Killer T Cells ◽  
Α Chain ◽  
Killer T Cells ◽  
Deficient Mice ◽  
Natural Killer T

scholarly journals CD1d-restricted Human Natural Killer T Cells Are Highly Susceptible to Human Immunodeficiency Virus 1 Infection

2002 ◽  
Vol 195 (7) ◽  
pp. 869-879 ◽  
Author(s):  
Alison Motsinger ◽  
David W. Haas ◽  
Aleksandar K. Stanic ◽  
Luc Van Kaer ◽  
Sebastian Joyce ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Natural Killer ◽  
Cell Receptor ◽  
Nkt Cells ◽  
Immunodeficiency Virus ◽  
Nk T Cells ◽  
Killer T Cells ◽  
Hiv 1

Human natural killer (NK) T cells are unique T lymphocytes that express an invariant T cell receptor (TCR) Vα24-Vβ11 and have been implicated to play a role in various diseases. A subset of NKT cells express CD4 and hence are potential targets for human immunodeficiency virus (HIV)-1 infection. We demonstrate that both resting and activated human Vα24+ T cells express high levels of the HIV-1 coreceptors CCR5 and Bonzo (CXCR6), but low levels of CCR7, as compared with conventional T cells. Remarkably NKT cells activated with α-galactosylceramide (α-GalCer)-pulsed dendritic cells were profoundly more susceptible to infection with R5-tropic, but not X4-tropic, strains of HIV-1, compared with conventional CD4+ T cells. Furthermore, resting CD4+ NKT cells were also more susceptible to infection. After initial infection, HIV-1 rapidly replicated and depleted the CD4+ subset of NKT cells. In addition, peripheral blood NKT cells were markedly and selectively depleted in HIV-1 infected individuals. Although the mechanisms of this decline are not clear, low numbers or absence of NKT cells may affect the course of HIV-1 infection. Taken together, our findings indicate that CD4+ NKT cells are directly targeted by HIV-1 and may have a potential role during viral transmission and spread in vivo.

CD4+ Invariant T-Cell–Receptor+ Natural Killer T Cells in Bronchial Asthma

2006 ◽  
Vol 354 (11) ◽  
pp. 1117-1129 ◽  
Author(s):  
Omid Akbari ◽  
John L. Faul ◽  
Elisabeth G. Hoyte ◽  
Gerald J. Berry ◽  
Jan Wahlström ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Natural Killer ◽  
T Cell Receptor ◽  
Bronchial Asthma ◽  
Cell Receptor ◽  
Natural Killer T Cells ◽  
Killer T Cells ◽  
Natural Killer T
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