Activation of natural killer T cells by α-galactosylceramide in the presence of CD1d provides protection against colitis in mice

Saubermann, Lawrence J.; Beck, Paul L.; Jong, Ype P. de; Pitman, Richard S.; Ryan, Mark; Snapper, Scott B.; Hagen, Susan J.; Kanauchi, Osamu; Motoki, Kazuhiro; Sakai, Teruyuki; Terhorst, Cox; Koezuka, Yasuhiko; Podolsky, Daniel K.; Blumberg, Richard S.; Exley, Mark A.; Balk, Steven P.

doi:10.1053/gast.2000.9114

Cited by 206 publications

(147 citation statements)

References 39 publications

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“…␣-ManCer had been reported to have no agonist activity (14,35,36). Consistent with this result, we found that tetramers of ␣-ManCer͞CD1d did not stain V␣14i NKT cells, and ␣-ManCer only poorly stimulated V␣14i NKT cell hybridomas and did not cause IL-4 release in vivo.…”

Section: Discussionsupporting

confidence: 89%

The T cell antigen receptor expressed by Vα14iNKT cells has a unique mode of glycosphingolipid antigen recognition

Sidobre

Hammond

Bénazet-Sidobre

et al. 2004

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

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Natural killer (NK) T cells with an invariant V␣14 rearrangement (V␣14i) are the largest population of lipid antigen-specific T lymphocytes identified in animals. They react to the glycolipid ␣-galactosyl ceramide (␣-GalCer) presented by CD1d, and they may have important regulatory functions. It was previously shown that the V␣14i T cell antigen receptor (TCR) has a high affinity for the ␣-GalCer͞CD1d complex, driven by a long half-life (t 1/2 ). Although this result could have reflected the unique attributes of ␣-GalCer, using several related glycolipid compounds, we show here that the threshold for full activation of V␣14i NKT cells by these glycosphingolipids requires a relatively high-affinity TCR interaction with a long t 1/2. Furthermore, our data are consistent with the view that the mechanism of recognition of these compounds presented by CD1d to the V␣14i NKT cell TCR is likely to fit a lock-and-key model. Overall, these findings emphasize the distinct properties of glycosphingolipid antigen recognition by V␣14i NKT cells.

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Section: Discussionsupporting

confidence: 89%

The T cell antigen receptor expressed by Vα14iNKT cells has a unique mode of glycosphingolipid antigen recognition

Sidobre

Hammond

Bénazet-Sidobre

et al. 2004

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

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“…A CD25 ϩ subset of these cells appears to suppress activity of colitigenic cells already deployed in the lamina propria (3,35,50). As noted above, other T cell subsets [intraepithelial CD8 ϩ (5, 6), CD4 ϩ CD8 ϩ (7, 9), or NKT (11,45) cells] also confer colitis resistance in some settings. At this juncture, it is not yet clear how B cell-dependent expansion of these central or mucosal T cell populations may reduce colitigenic CD4 ϩ T cell activity.…”

Section: Discussionmentioning

confidence: 88%

“…NKT cells in some settings suppress immune inflammation, including intraocular inflammation (15) and certain models of colitis (11,45). The mechanism for this protection is uncertain.…”

Section: Discussionmentioning

confidence: 99%

Mesenteric B cells centrally inhibit CD4⁺T cell colitis through interaction with regulatory T cell subsets

Wei

Velázquez

Turovskaya

et al. 2005

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

166

130

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“…Consequently, NKT cells have been implicated in a number of diverse immunological processes, including tumor responses, clearance of pathogens, regulation of autoimmunity, and tolerance induction (20 -23). Treatment with ␣-GalCer or ␣-GalCer-loaded dendritic cells (DC) induces a potent antitumor response by stimulating IFN-␥ production (24 -26), while ␣-GalCer has also been shown to ameliorate autoimmunity through the induction of Th2 responses (27)(28)(29). In contrast to the ability of ␣-GalCer to generate both Th1 and Th2 cytokines, OCH, a truncated derivative of ␣-GalCer, induces a preferential Th2 response that can suppress experimental autoimmune encephalitis and collagen-induced arthritis (30,31), whereas the C-glycoside derivative ␣-C-GalCer induces a selective Th1 response and is very effective at preventing tumor metastasis (32).…”

mentioning

confidence: 99%

Critical Role for the Chemokine Receptor CXCR6 in Homeostasis and Activation of CD1d-Restricted NKT Cells

Germanov¹,

Veinotte²,

Cullen³

et al. 2008

The Journal of Immunology

103

109

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NK T (NKT) cells play important roles in the regulation of diverse immune responses. However, little is known about the mechanisms that regulate homeostasis and activation of these cells. Thymic NKT cells up-regulated the chemokine receptor CXCR6 following positive selection and migrated toward CXCL16 in vitro. However, CXCR6 was not essential for thymic development or maturation. In contrast, liver and lung NKT cells were depleted in CXCR6+/− and CXCR6−/− mice. The reduction in liver and lung NKT cells coincided with an increase in bone marrow NKT cells, suggesting a redistribution of NKT cells in CXCR6−/− animals. In wild-type mice, CXCL16 neutralization reduced accumulation of mature NK1.1+, but not immature NK1.1− NKT cell recent thymic emigrants in the liver. Given that thymic NKT cells are preferentially exported as NK1.1− cells, this suggests an additional role for CXCR6/CXCL16 in maturation or survival of immature liver NKT cells. CXCL16 blockade did not deplete resident NK1.1+ NKT cells, indicating that CXCR6/CXCL16 are not required to retain mature NKT cells in the liver. Cytokine production by liver and spleen NKT cells was impaired in CXCR6−/− mice following in vivo stimulation with α-galactosylceramide, implicating a novel role for CXCR6 in NKT cell activation. Reduced IFN-γ production was not due to an intrinsic defect as production was normal following PMA and ionomycin stimulation. Preformed transcripts for IL-4, but not IFN-γ, were reduced in CXCR6−/− liver NKT cells. These data identify critical roles for CXCR6/CXCL16 in NKT cell activation and the regulation of NKT cell homeostasis.

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Activation of natural killer T cells by α-galactosylceramide in the presence of CD1d provides protection against colitis in mice

Cited by 206 publications

References 39 publications

The T cell antigen receptor expressed by Vα14iNKT cells has a unique mode of glycosphingolipid antigen recognition

The T cell antigen receptor expressed by Vα14iNKT cells has a unique mode of glycosphingolipid antigen recognition

Mesenteric B cells centrally inhibit CD4⁺T cell colitis through interaction with regulatory T cell subsets

Critical Role for the Chemokine Receptor CXCR6 in Homeostasis and Activation of CD1d-Restricted NKT Cells

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Activation of natural killer T cells by α-galactosylceramide in the presence of CD1d provides protection against colitis in mice

Cited by 206 publications

References 39 publications

The T cell antigen receptor expressed by Vα14iNKT cells has a unique mode of glycosphingolipid antigen recognition

The T cell antigen receptor expressed by Vα14iNKT cells has a unique mode of glycosphingolipid antigen recognition

Mesenteric B cells centrally inhibit CD4+T cell colitis through interaction with regulatory T cell subsets

Critical Role for the Chemokine Receptor CXCR6 in Homeostasis and Activation of CD1d-Restricted NKT Cells

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Mesenteric B cells centrally inhibit CD4⁺T cell colitis through interaction with regulatory T cell subsets