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NKT cells: what's in a name?

Abstract

Recent years have seen so-called natural killer T (NKT) cells emerge as important regulators of the immune response. The existence of NKT-cell subsets, and other types of T cell that resemble NKT cells, is an ongoing source of confusion in the literature. This perspective article seeks to clarify which cells fall under the NKT-cell umbrella, and which might be best considered as separate.

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Figure 1: Development of type I NKT cells in mice.

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Acknowledgements

We thank many colleagues in the NKT cell and related fields for stimulating discussions that were helpful in writing this opinion article. This work was supported by the National Health and Medical Research Council of Australia, The Human Frontiers Science Program and The National Institutes of Health.

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Correspondence to Dale I. Godfrey.

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DATABASES

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CD4

CD8

CD95L

CD161

GM-CSF

IFN-γ

IL-2

IL-4

IL-13

Nkrp1c

TNF

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Glossary

α-GALACTOSYLCERAMIDE

(α-GalCer). A synthetic or marine-sponge-derived glycolipid containing α-anomeric glycosidic linkage of the galactose residue to the sphingosine base. This, and structurally related lipids, potently activate CD1d-restricted natural killer T (NKT) cells that express the semi-invariant Vα14-Jα18 T-cell receptor (TCR) in mice (and the Vα24-Jα18+ equivalent cells in humans)101.

α-GALCER-LOADED CD1D TETRAMERS

A complex of four CD1d molecules loaded with α-GalCer that has sufficient affinity to detect cell-surface expression of the semi-invariant TCR expressed by NKT cells in mice (Vα14-Jα18+) and humans (Vα24-Jα18+) using flow cytometry.

CORTICAL THYMIC EPITHELIAL CELLS

Epithelial cells found in the outer region or cortex of thymic lobules. These cells are crucial for the positive selection of conventional MHC class-I- and class-II-restricted T cells, but not for the positive selection of CD1d-restricted NKT cells.

DOUBLE-POSITIVE THYMOCYTES

Immature T cells in the thymus that are characterized by the expression of both the CD4 and CD8 co-receptor proteins. They represent the majority (80–90%) of thymocytes. These cells express CD1d molecules and have been implicated in the positive selection of NKT cells.

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Godfrey, D., MacDonald, H., Kronenberg, M. et al. NKT cells: what's in a name?. Nat Rev Immunol 4, 231–237 (2004). https://doi.org/10.1038/nri1309

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