CD1d Ligands: The Good, the Bad, and the Ugly

Brutkiewicz, Randy R.

doi:10.4049/jimmunol.177.2.769

Cited by 161 publications

(134 citation statements)

References 95 publications

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“…It is well documented that glycolipids, including GPI's from T. brucei, can be presented in the context of CD1d, expressed on APCs, resulting in the activation of CD1d-restricted T cells (27,48,49). Therefore, the possible involvement of the CD1d-mediated pathways in the protective effects observed in GPI-based treated/infected animals was envisaged and evaluated using CD1d Ϫ/Ϫ mice.…”

Section: The Protective Effect Of the Gpi-based Treatment During T Bmentioning

confidence: 99%

A Glycosylphosphatidylinositol-Based Treatment Alleviates Trypanosomiasis-Associated Immunopathology

Stijlemans

Baral

Guilliams

et al. 2007

The Journal of Immunology

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The GPI-anchored trypanosome variant surface glycoprotein (VSG) triggers macrophages to produce TNF, involved in trypanosomiasis-associated inflammation and the clinical manifestation of sleeping sickness. Aiming at inhibiting immunopathology during experimental Trypanosoma brucei infections, a VSG-derived GPI-based treatment approach was developed. To achieve this, mice were exposed to the GPI before an infectious trypanosome challenge. This GPI-based strategy resulted in a significant prolonged survival and a substantial protection against infection-associated weight loss, liver damage, acidosis, and anemia; the latter was shown to be Ab-independent and correlated with reduced macrophage-mediated RBC clearance. In addition, GPI-based treatment resulted in reduced circulating serum levels of the inflammatory cytokines TNF and IL-6, abrogation of infection-induced LPS hypersensitivity, and an increase in circulating IL-10. At the level of trypanosomiasis-associated macrophage activation, the GPI-based treatment resulted in an impaired secretion of TNF by VSG and LPS pulsed macrophages, a reduced expression of the inflammatory cytokine genes TNF, IL-6, and IL-12, and an increased expression of the anti-inflammatory cytokine gene IL-10. In addition, this change in cytokine pattern upon GPI-based treatment was associated with the expression of alternatively activated macrophage markers. Finally, the GPI-based treatment also reduced the infection-associated pathology in Trypanosoma congolense and Trypanosoma evansi model systems as well as in tsetse fly challenge experiments, indicating potential field applicability for this intervention strategy.

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Section: The Protective Effect Of the Gpi-based Treatment During T Bmentioning

confidence: 99%

A Glycosylphosphatidylinositol-Based Treatment Alleviates Trypanosomiasis-Associated Immunopathology

Stijlemans

Baral

Guilliams

et al. 2007

The Journal of Immunology

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“…20 Those CD1d-restricted NKT cells that express another TCRa chain are simply designated 'non-canonical' or 'variant'. 20 The presentation of antigens by CD1d molecules stimulates NKT cells which can mediate perforin-dependent cytotoxicity. The upregulation of CD40L on activated NKT cells leads to the production of interleukin-12 (IL-12) by dendritic cells (DC), 21 and IL-12 activates NKT cells to produce interferon-c (IFN-c), which, in turn, stimulates NK cells and CD8 + cytotoxic T Lymphocytes (CTL).…”

Section: Introductionmentioning

confidence: 99%

Apoptosis‐induced inhibition of CD1d‐mediated antigen presentation: different roles for caspases and signal transduction pathways

et al. 2008

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SummaryThe stimulation of programmed cell death can either enhance or inhibit antigen presentation by classic major histocompatibility complex molecules. In the current study, we report that the induction of apoptosis by topoisomerase I inhibition or elevation of intracellular ceramide levels substantially impairs CD1d-mediated antigen presentation. In the former case, such a reduction occurred via the regulation of both the p38 mitogen-activated protein kinases and protein kinase C d signal transduction pathways as well as the caspase cascade, whereas the latter was p38-(but not caspase)-dependent. Confocal microscopic analysis showed an altered intracellular distribution of CD1d following the inhibition topoisomerase I or by an increase in intracellular ceramide levels, that was prevented by p38 and caspase inhibitors. Thus, the induction of apoptosis in antigen presenting cells severely compromises CD1d-mediated antigen presentation by multiple mechanisms.

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“…Stimulation of type I NKT cells results in the rapid production of cytokines, including IFN-␥ and IL-4. Although a number of endogenous and pathogen-derived ligands capable of activating type I NKT cells have been described (8), the prototypical ligand remains ␣-galactosylceramide (␣-GalCer) that was originally isolated from the marine sponge Agelas mauritianus (9). ␣-GalCer-CD1d tetramers can be used to specifically identify type I NKT cells in mice and humans (10).…”

mentioning

confidence: 99%

Polymorphisms in CD1d affect antigen presentation and the activation of CD1d-restricted T cells

Zimmer

Nguyen²,

Wang³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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CD1 proteins constitute a distinct lineage of antigen-presenting molecules specialized for the presentation of lipid antigens to T cells. In contrast to the extensive sequence polymorphism characteristic of classical MHC molecules, CD1 proteins exhibit limited sequence diversity. Here, we describe the identification and characterization of CD1d alleles in wild-derived mouse strains. We demonstrate that polymorphisms in CD1d affect the presentation of endogenous and exogenous ligands to CD1d-restricted T cells, including type I (V␣14i) and type II (non-V␣14i) natural killer T (NKT) cells. Using congenic mice, we found CD1d polymorphisms affect the thymic selection of type I NKT cells and induce allogeneic T cell responses. Collectively, results from these studies demonstrate a role for polymorphisms in influencing the development and function of CD1d-restricted T cells.T cell activation ͉ T cell development

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CD1d Ligands: The Good, the Bad, and the Ugly

Cited by 161 publications

References 95 publications

A Glycosylphosphatidylinositol-Based Treatment Alleviates Trypanosomiasis-Associated Immunopathology

A Glycosylphosphatidylinositol-Based Treatment Alleviates Trypanosomiasis-Associated Immunopathology

Apoptosis‐induced inhibition of CD1d‐mediated antigen presentation: different roles for caspases and signal transduction pathways

Polymorphisms in CD1d affect antigen presentation and the activation of CD1d-restricted T cells

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