Immunomodulatory Type II Natural Killer T Lymphocytes in Health and Disease

Rhost, Sara; Sedimbi, Saikiran K.; Kadri, Nadir; Cardell, Susanna

doi:10.1111/j.1365-3083.2012.02750.x

Cited by 65 publications

(94 citation statements)

References 77 publications

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“…It is interesting that sulfatide-reactive CD1d-restricted T cells expressing TCR␥␦ were recently described in human peripheral blood lymphocytes (49). Sulfatide-reactive CD1d-restricted TCR␥␦ cells have not been described in mice, and the sulfatide-reactive T cells hitherto described in mice carry TCR␣␤ (8); however, we cannot exclude a contribution by sulfatide-specific, CD1d-restricted TCR␥␦ T cells in our study.…”

Section: Figcontrasting

confidence: 41%

“…1A). Type II NKT cells cannot be identified with certainty by surface markers (8) aureus-infected mice. Data are pooled from two separate experiments, and each symbol represents the value from one mouse.…”

Section: Resultsmentioning

confidence: 99%

“…Severe sepsis can lead to disseminated intravascular coagulation (DIC), multiorgan failure, and death (6). Natural killer T (NKT) cells are a subset of T lymphocytes restricted by the CD1d glycoprotein, a major histocompatibility complex (MHC) class I-like molecule (7,8). Unlike most T cells, NKT cells do not recognize protein antigens but instead recognize lipid and glycolipid antigens presented on CD1d.…”

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confidence: 99%

“…NKT cells are divided into two types (13): type I NKT cells (also known as invariant NKT, or iNKT, cells) express an invariant V␣14-J␣18 (in mice) or V␣24-J␣18 (in humans) ␣-chain of the T-cell receptor (TCR), whereas type II NKT cells use a diverse TCR repertoire. The two types of NKT cells have been shown to display different, or even opposite, activities in immune responses (8). A subset of type II NKT cells recognizes sulfatide (a self-glycosphingolipid derived from myelin) presented on CD1d (14)(15)(16).…”

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confidence: 99%

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Sulfatide Attenuates Experimental Staphylococcus aureus Sepsis through a CD1d-Dependent Pathway

et al. 2013

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Natural killer T (NKT) lymphocytes are implicated in the early response to microbial infection. Further, sulfatide, a myelin selfglycosphingolipid, activates a type II NKT cell subset and can modulate disease in murine models. We examined the role of NKT cells and the effect of sulfatide treatment in a murine model of Staphylococcus aureus sepsis. The lack of CD1d-restricted NKT cells did not alter survival after a lethal inoculum of S. aureus. In contrast, sulfatide treatment significantly improved the survival rate of mice with S. aureus sepsis, accompanied by decreased levels of tumor necrosis factor alpha and interleukin-6 in the blood. The protective effect of sulfatide treatment depended on CD1d but not on type I NKT cells, suggesting that activation of type II NKT cells by sulfatide has beneficial effects on the outcome of S. aureus sepsis in this model.

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Section: Figcontrasting

confidence: 41%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Sulfatide Attenuates Experimental Staphylococcus aureus Sepsis through a CD1d-Dependent Pathway

et al. 2013

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“…iNKT cells display an effector/ memory phenotype and rapidly secrete large amounts of cytokines following primary stimulation. In contrast, CD1d-restricted NKT cells that use diverse TCR α-and β-chains have also been identified, although recurrent use of certain germ-line segments has been observed (4)(5)(6)(7)(8). These NKT cells are referred to as type II or diverse NKT (dNKT) cells.…”

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confidence: 99%

Recognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs

Tatituri

Watts

Bhowruth

et al. 2013

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

106

112

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CD1d-restricted natural killer T (NKT) cells include two major subgroups. The most widely studied are Vα14Jα18 + invariant NKT (iNKT) cells that recognize the prototypical α-galactosylceramide antigen, whereas the other major group uses diverse T-cell receptor (TCR) α-and β-chains, does not recognize α-galactosylceramide, and is referred to as diverse NKT (dNKT) cells. dNKT cells play important roles during infection and autoimmunity, but the antigens they recognize remain poorly understood. Here, we identified phosphatidylglycerol (PG), diphosphatidylglycerol (DPG, or cardiolipin), and phosphatidylinositol from Mycobacterium tuberculosis or Corynebacterium glutamicum as microbial antigens that stimulated various dNKT, but not iNKT, hybridomas. dNKT hybridomas showed distinct reactivities for diverse antigens. Stimulation of dNKT hybridomas by microbial PG was independent of Toll-like receptor-mediated signaling by antigen-presenting cells and required lipid uptake and/or processing. Furthermore, microbial PG bound to CD1d molecules and plate-bound PG/CD1d complexes stimulated dNKT hybridomas, indicating direct recognition by the dNKT cell TCR. Interestingly, despite structural differences in acyl chain composition between microbial and mammalian PG and DPG, lipids from both sources stimulated dNKT hybridomas, suggesting that presentation of microbial lipids and enhanced availability of stimulatory self-lipids may both contribute to dNKT cell activation during infection.

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CD1d ‐Restricted Natural Killer T Cells

Hill

Bezbradica

Kaer

et al. 2016

Encyclopedia of Life Sciences

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Natural killer T (NKT) cells that express the semi‐invariant T‐cell receptor are innate‐like lymphocytes whose functions are controlled by self and foreign glycolipid ligands. Such ligands are presented by the antigen‐presenting, MHC class I‐like molecule CD1d, which belongs to a family of lipid antigen‐presenting molecules collectively called CD1. Activation of NKT cells in vivo results in rapid release of copious amounts of effector cytokines and chemokines with which they regulate innate and adaptive immune responses to pathogens, certain types of cancers and self‐antigens. The nature of CD1d‐restricted ligands, the manners in which they are recognised and the unique effector functions of NKT cells suggest an immunoregulatory role for this T‐cell subset. Their ability to respond fast and our ability to steer NKT cell cytokine responses to altered lipid ligands make them an important target for vaccine design and immunotherapies against autoimmune diseases. This article summarises our current understanding of CD1d‐restricted NKT cell biology and how these innate‐like lymphocytes control inflammation. Key Concepts CD1d molecules belong to a family of lipid antigen‐presenting molecules collectively called CD1. CD1d molecules resemble peptide antigen‐presenting MHC class I molecules. CD1d molecules restrict the specificity and functions of Natural killer T (NKT) cells. NKT cells recognise self‐ and nonself‐lipid ligands. Antigen recognition quickly activates NKT cells, which respond immediately by releasing proinflammatory and immunoregulatory cytokines and chemokines. Activated NKT cells communicate with cells of the innate and adaptive immune systems by cell–cell interactions and/or via soluble mediators. Such communications allow NKT cells to control immune responses to microbial pathogens and certain cancers. NKT‐cell activation has beneficial and, sometimes, adverse effects on certain autoimmune and metabolic disorders. NKT cells are targets for vaccine adjuvants and immunotherapies.

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Immunomodulatory Type II Natural Killer T Lymphocytes in Health and Disease

Cited by 65 publications

References 77 publications

Sulfatide Attenuates Experimental Staphylococcus aureus Sepsis through a CD1d-Dependent Pathway

Sulfatide Attenuates Experimental Staphylococcus aureus Sepsis through a CD1d-Dependent Pathway

Recognition of microbial and mammalian phospholipid antigens by NKT cells with diverse TCRs

CD1d ‐Restricted Natural Killer T Cells

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