The response of natural killer T cells to glycolipid antigens is characterized by surface receptor down-modulation and expansion

Wilson, Michael T.; Johansson, Cecilia; Olivares–Villagómez, Danyvid; Singh, Avneesh K.; Stanic, Aleksandar K.; Wang, Chyung Ru; Joyce, Sebastian; Wick, Mary Jo; Kaer, Luc Van

doi:10.1073/pnas.1833166100

Cited by 308 publications

(366 citation statements)

References 35 publications

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“…Recovery numbers of HL were also increased by day 4 of L. monocytogenes infection and slightly, though not significantly, elevated by a-GalCer treatment (data not shown). Consistent with previous findings [57][58][59][60][61][62][63][64][65], a-GalCer/CD1d tetramer-reactive (a-GalCer/CD1d 1 ) T cells became undetectable on day 1 after a-GalCer treatment and then re-emerged, though incompletely, by day 4 ( Fig. 2A, Table 1).…”

Section: Liversupporting

confidence: 92%

“…Because IL-4 and IFN-g are secreted by iNKT cells after a-GalCer treatment [24], secretion of both cytokines was analyzed, in addition. Frequencies of cytokine-secreting cells were analyzed 1 h after a-GalCer treatment for the following reasons: (i) mice were treated with a-GalCer 2 h before infection, (ii) iNKT cells become undetectable immediately after a-GalCer treatment [58][59][60], (iii) numerical increase of Gr-1 1 cells in the liver was already observed 2 h after a-GalCer treatment (see Fig. 5, Table 2).…”

Section: Monocytogenes-induced Inflammation In the Liver And Spleementioning

confidence: 99%

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Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1⁺ cells into the liver

Emoto

Yoshizawa

et al. 2010

Eur J Immunol

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a-Galactosylceramide (a-GalCer) activates invariant (i)NKT cells, which in turn stimulate immunocompetent cells. Although activation of iNKT cells appears critical for regulation of immune responses, it remains elusive whether protection against intracellular bacteria can be induced by a-GalCer. Here, we show that a-GalCer treatment ameliorates murine listeriosis, and inhibits inflammation following Listeria monocytogenes infection. Liver infiltration of Gr-1 1 cells and c/d T cells was accelerated by a-GalCer treatment. Gr-1 1 cell and c/d T-cell depletion exacerbated listeriosis in a-GalCer-treated mice, and this effect was more pronounced after depletion of Gr-1 1 cells than that of c/d T cells. Although GM-CSF and IL-17 were secreted by NKT cells after a-GalCer treatment, liver infiltration of Gr-1 1 cells was not prevented by neutralizing mAb. In parallel to the numerical increase of CD11b 1 Gr-1 1 cells in the liver following a-GalCer treatment, CD11b À Gr-1 1 cells were numerically reduced in the bone marrow. In addition, respiratory burst in Gr-1 1 cells was enhanced by a-GalCer treatment. Our results indicate that a-GalCer-induced antibacterial immunity is caused, in part, by accelerated infiltration of Gr-1 1 cells and to a lesser degree of c/d T cells into the liver. We also suggest that the infiltration of Gr-1 1 cells is caused by an accelerated supply from the bone marrow.Key words: a-galactosylceramide . L. monocytogenes . NKT cell Supporting Information available online IntroductionListeria monocytogenes is a Gram-positive facultative intracellular bacterial pathogen, which causes disseminated infection in immunocompromised hosts [1]. Experimental murine listeriosis is instrumental in elucidating host defense mechanisms against intracellular bacteria. Cells of the innate immune system play a pivotal role as a first line of defense against L. monocytogenes [2-5] and among these, Gr-1 1 cells are central for the elimination of this pathogen at early stages of infection [6][7][8]. Numerous cytokines such as GM-CSF, IL-3, IL-6, IL-11, and SCF promote granulopoiesis by themselves and/or in concert with G-CSF [9,10]. G-CSF is indispensable for both steady-state and emergency granulopoiesis [11][12][13][14], and IL-17 regulates G-CSF secretion [9,10,[15][16][17][18]. In addition to Gr-1 1 cells, g/d T cells also participate in early protection against 1328L. monocytogenes infection [19][20][21][22]. The vast majority of L. monocytogenes organisms are trapped in the liver immediately after systemic infection [23] and hence, immunocompetent cells that reside in, and/or migrate into, the liver are critical for infection control.NKT cells represent a unique subset of T lymphocytes, which are characterized by the co-expression of NK cell markers such as NKR-P1B/C (NK1.1; CD161) [24]. In the mouse, the majority of NKT cells express an invariant (i) TCR composed of Va14/Ja18 gene segments, i.e. iNKT cells [24]. In contrast to conventional T cells, which recognize peptide antigens presented by polymorphic MHC ...

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Section: Liversupporting

confidence: 92%

Section: Monocytogenes-induced Inflammation In the Liver And Spleementioning

confidence: 99%

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1⁺ cells into the liver

Emoto

Yoshizawa

et al. 2010

Eur J Immunol

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“…In parallel to these changes, iNKT cell-surface receptors, including TCR and NK1.1, become donwregulated, which render iNKT cells invisible by flow-cytometric detection [19,27]. The downregulation of TCR remains until at least 24 hr.…”

Section: Activation Of Inkt Cells By αGc In the Heartmentioning

confidence: 99%

“…Then, iNKT cells rapidly proliferate and increase to the peak level 72 hr after αGC administration. The activation of iNKT cells by αGC has been observed in various organs, such as spleen, liver, lung, and kidney [18,19,[27][28][29].…”

Section: Activation Of Inkt Cells By αGc In the Heartmentioning

confidence: 99%

Activation of invariant natural killer T cells by α-galactosylceramide ameliorates myocardial ischemia/reperfusion injury in mice

Homma¹,

Kinugawa²,

Takahashi³

et al. 2013

Journal of Molecular and Cellular Cardiology

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“…14,17 Moreover, multiple injections of soluble aGalCer induced an anergy state in NKT cells in murine tumor-bearing models 18,19 or a shift from Th1-to Th2-type cytokine production. 20,21 Indeed, a phase I clinical study involving i.v. injection of aGalCer into advanced cancer patients resulted in neither Va24 1 NKT cell expansion nor clinical responses, although feasibility was proved.…”

mentioning

confidence: 99%

Dendritic cell maturation by CD11c⁻ T cells and Vα24⁺ natural killer T‐cell activation by α‐Galactosylceramide

Ishikawa¹,

Motohashi²,

Ishikawa³

et al. 2005

Intl Journal of Cancer

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Human invariant Vα24+ natural killer T (NKT) cells display potent antitumor activity upon stimulation. Activation of endogenous Vα24+ NKT cells would be one strategy for the treatment of cancer patients. For example, dendritic cells (DCs) loaded with a glycolipid NKT cell ligand, α‐galactosylceramide (αGalCer, KRN7000), are a possible tool for the activation and expansion of functional Vα24+ NKT cells in vivo. In this report, we demonstrate that the levels of expansion and the ability to produce IFN‐γ of Vα24+ NKT cells induced by αGalCer‐loaded whole PBMCs cultured with IL‐2 and GM‐CSF (IL‐2/GM‐CSF‐cultured PBMCs) were superior to those of cells induced by monocyte‐derived CD11c+ DCs (moDCs) developed with IL‐4 and GM‐CSF. Interestingly, CD11c+ cells in the IL‐2/GM‐CSF‐cultured PBMCs showed a mature phenotype without further stimulation and exerted potent stimulatory activity on Vα24+ NKT cells to enable them to produce IFN‐γ preferentially at an extent equivalent to mature moDCs induced by stimulation with LPS or a cytokine cocktail. Cocultivation with CD11c− cells in the IL‐2/GM‐CSF‐cultured PBMCs induced maturation of moDCs. In particular, CD11c−CD3+ T cells appeared to play important roles in DC maturation. In addition, TNF‐α was preferentially produced by CD11c−CD3+ T cells in IL‐2/GM‐CSF‐cultured PBMCs and was involved in the maturation of moDCs. Thus, the maturation of DCs induced by CD11c− T cells through TNF‐α production appears to result in the efficient expansion and activation of Vα24+ NKT cells to produce IFN‐γ preferentially. © 2005 Wiley‐Liss, Inc.

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The response of natural killer T cells to glycolipid antigens is characterized by surface receptor down-modulation and expansion

Abstract: CD1d-restricted natural killer T (NKT

Cited by 308 publications

References 35 publications

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1⁺ cells into the liver

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1⁺ cells into the liver

Activation of invariant natural killer T cells by α-galactosylceramide ameliorates myocardial ischemia/reperfusion injury in mice

Dendritic cell maturation by CD11c⁻ T cells and Vα24⁺ natural killer T‐cell activation by α‐Galactosylceramide

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The response of natural killer T cells to glycolipid antigens is characterized by surface receptor down-modulation and expansion

Abstract: CD1d-restricted natural killer T (NKT

Cited by 308 publications

References 35 publications

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1+ cells into the liver

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1+ cells into the liver

Activation of invariant natural killer T cells by α-galactosylceramide ameliorates myocardial ischemia/reperfusion injury in mice

Dendritic cell maturation by CD11c− T cells and Vα24+ natural killer T‐cell activation by α‐Galactosylceramide

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Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1⁺ cells into the liver

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1⁺ cells into the liver

Dendritic cell maturation by CD11c⁻ T cells and Vα24⁺ natural killer T‐cell activation by α‐Galactosylceramide