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The Journal of Immunology, 1999, 163: 2373-2377.
Copyright © 1999 by The American Association of Immunologists


CUTTING EDGE

Cutting Edge: Activation of NK T Cells by CD1d and {alpha}-Galactosylceramide Directs Conventional T Cells to the Acquisition of a Th2 Phenotype

Nagendra Singh*, Seokmann Hong*, David C. Scherer1,*, Isao Serizawa{dagger}, Nicolas Burdin{ddagger}, Mitchell Kronenberg{ddagger}, Yasuhiko Koezuka{dagger} and Luc Van Kaer2,*

* Howard Hughes Medical Institute, Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232; {dagger} Pharmaceutical Research Laboratory, Kirin Brewery Co, Ltd., Takasaki-shi, Gunma, Japan; and {ddagger} Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121


    Abstract
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
NK T cells recognize glycolipid Ags such as {alpha}-galactosylceramide ({alpha}-GalCer) presented by the MHC class I-like molecule CD1d. In this paper we have studied the in vivo effects of {alpha}-GalCer on the generation of adaptive immune responses. Treatment of mice with {alpha}-GalCer resulted in rapid activation of NK T cells and production of the cytokines IL-4 and IFN-{gamma}. However, after this initial stimulation, NK T cells became polarized for the production of IL-4. Further, as soon as 6 days after {alpha}-GalCer injection, a marked increase in serum IgE levels was observed. Administration of {alpha}-GalCer at the time of priming of mice with protein Ag resulted in the generation of Ag-specific Th2 cells and a profound increase in the production of IgE. Collectively, these findings indicate that {alpha}-GalCer may be useful for modulating immune responses toward a Th2 phenotype during prophylaxis and therapy.


    Introduction
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Natural killer T cells represent an unusual group of T lymphocytes that share receptor structures with conventional T cells and NK cells (1, 2). NK T cells express intermediate levels of a semiinvariant TCR (V{alpha}14-J{alpha}281 paired with Vß8.2, 7, or 2 in mouse), together with NK cell receptors (NKR-P1 and Ly-49 in mouse). These cells are found in the thymus, spleen, liver, and bone marrow, but are rare in lymph nodes and the gut. Unlike conventional T cells that recognize peptide Ags presented by the classical MHC class I or class II molecules, NK T cells are specific for glycolipid Ags bound with the MHC class I-like molecule CD1d (1, 2, 3, 4, 5, 6). Expression of CD1d is required for the development of NK T cells (7, 8, 9, 10). When stimulated through their TCR, NK T cells quickly produce a variety of cytokines, including large amounts of IL-4 and significant amounts of IFN-{gamma} (1, 2). It was therefore postulated that NK T cells may influence the differentiation of naive CD4+ T lymphocytes into functional Th cells (11). However, deletion of ß2-microglobulin or CD1d molecules in mice did not affect the differentiation of conventional CD4+ T cells into Th cells with distinct functions (8, 9, 10, 12, 13, 14), indicating that NK T cells are not absolutely required for the generation of polarized Th responses.

The glycolipid {alpha}-galactosylceramide ({alpha}-GalCer)3 was originally isolated as a natural product from marine sponges (15, 16). Several studies demonstrated that NK T cells specifically recognize this natural product and its synthetic homologue (KRN7000) and that this recognition requires expression of CD1d (2, 4). Further studies indicated that reactivity to {alpha}-GalCer is highly specific for NK T cells that express the invariant V{alpha}14-J{alpha}281 TCR in mice (17). In vitro stimulation of mouse spleen cells by synthetic {alpha}-GalCer results in proliferation of NK T cells and production of both IFN-{gamma} and IL-4 (2, 4, 17).

In this report we have studied the in vivo effects of {alpha}-GalCer on the production of cytokines and the generation of an adaptive immune response. Our results demonstrate that {alpha}-GalCer directs the differentiation of naive T cell precursors toward the development of a Th2 phenotype. These findings indicate that NK T cells can influence the Th1/Th2 balance and that in vivo treatment with {alpha}-GalCer may be useful for manipulating this balance during prophylaxis and therapy.


    Materials and Methods
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Mice

C57BL/6 mice were purchased from The Jackson Laboratory (Bar Harbor, ME). CD1d-deficient (9) mice and controls on a mixed C57BL/6 x 129 background or from the sixth backcross to C57BL/6 were bred in the animal facility at Vanderbilt University School of Medicine (Nashville, TN).

Antigens

{alpha}-GalCer (KRN7000) was chemically synthesized (18) and chicken OVA was purchased from Sigma (St. Louis, MO).

Flow cytometry

The following Abs were used for flow cytometry: anti-NK1.1-PE, anti-TCRß-cychrome, anti-CD69-FITC, anti-CD80-FITC, anti-CD86-FITC, and anti-B220-FITC (all from PharMingen, San Diego, CA). Stainings were performed by incubating cells with the Ab on ice in PBS plus 2% FCS, 0.1% azide, and anti-Fc{gamma}RIII Abs (clone 2.4.G2 from the American Type Culture Collection (ATCC), Manassas, VA) for 45 min. Cells were then washed and analyzed using a FACSCalibur flow cytometer (Becton Dickinson, San Jose, CA).

In vitro stimulation of splenocytes with {alpha}-GalCer

Splenocytes (4 x 105) were incubated with titrated amounts of {alpha}-GalCer in RPMI 1640 medium supplemented with 10% FCS, 50 µM 2-ME, 2 mM glutamine, antibiotics, and 10 mM HEPES (complete medium) for 72 h. For proliferation assays, 0.5 µCi of [3H]thymidine (NEN, Boston, MA) was then added to the wells, and after an additional 16 h of culture, cells were harvested with a cell harvester (Tomtec, Orange, CT), and uptake of radioactivity was measured with a betaplate reader (Wallac, Gaithersburg, MD). For measurement of cytokine levels, culture supernatants were collected and measured for IFN-{gamma} and IL-4 contents by ELISA.

Immunization of mice

{alpha}-GalCer (4 µg/mouse in 400 µl of vehicle) or vehicle (0.025% polysorbate-20 in PBS) were injected i.p. (2 µg) and i.v. (2 µg) into mice. Similar results were obtained when DMSO was used as the vehicle in which to dissolve {alpha}-GalCer. For immunization with OVA, mice were injected s.c. with OVA (100 µg/mouse) and {alpha}-GalCer (4 µg/mouse) or with OVA and vehicle emulsified in CFA (Becton Dickinson).

Measurement of Ag-specific T cell responses

Lymph node cells from immunized mice were depleted of CD8+, MHC class II+, and NK1.1+ cells by panning with anti-CD8 (clone 2.43; obtained from Dr. B. Graham, Vanderbilt University School of Medicine), anti-MHC class II (clone Y-3P from the ATCC), and anti-NK1.1 (clone PK136 from the ATCC) Abs, respectively, on plates coated with goat-anti mouse IgG (H+L) (Jackson ImmunoResearch Laboratories, West Grove, PA). These purified CD4+ T cells (3 x 105/well) were then cultured with 4 x 105 irradiated syngeneic spleen cells in the presence of graded doses of OVA Ag. After 60 h of culture, supernatants were collected for measurement of IFN-{gamma} and IL-4 by ELISA. After 72 h of culture, cells were pulsed with 0.5 µCi of [3H]thymidine, cultured for another 12 h, and uptake of radioactivity was measured as above.

RNase protection assay

Spleens were harvested from mice and total RNA was isolated (SV Total RNA Isolation System, Promega, Madison, WI). Cytokine levels were analyzed by RNase protection (RiboQuant multiprobe kit, mCK-1 probe set, PharMingen) using 5 µg of total RNA for each reaction. Protected fragments were visualized by autoradiography.

ELISA

A standard sandwich ELISA was used to measure mouse IFN-{gamma}, IL-4, and Ab isotype levels. IFN-{gamma}, IL-4, and total IgE were measured using purified and biotinylated Ab pairs and standards from PharMingen. For detection, streptavidin-HRP (HRP) conjugate (Zymed Laboratories, South San Francisco, CA) was used in conjunction with the substrate 3,3',5,'5'-tetramethylbenzidine (Dako, Carpinteria, CA). Ag-specific IgE levels were measured similarly, but plates were coated with 10 µg/ml of OVA instead of capture anti-IgE Ab. For measurement of Ag-specific IgM, IgG1 and IgG2a Abs immunoplates (Maxisorp, Nunc, Rochester, NY) were coated with 10 µg/ml of OVA in 0.1 M Na2HPO4. After blocking with 1% BSA in PBS, serial dilutions of antiserum were added. Detection was performed with anti-IgM-HRP, anti-IgG1-HRP, and anti-IgG2a-HRP Abs (all from Southern Biotechnology Associates, Birmingham, AL), in conjunction with the substrate o-phenylene-diamine (Sigma). Concentrations were calculated on the basis of standard curves of Ab isotypes (all from Southern Biotechnology Associates) run in parallel ELISA assays.


    Results
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Immunization of mice with {alpha}-GalCer results in the production of Th1 and Th2 cytokines and biases NK T cells for the production of Th2 cytokines

Previous in vitro studies have demonstrated that {alpha}-GalCer stimulates NK T cells to produce both IFN-{gamma} and IL-4 (2, 4, 17). We wanted to test whether {alpha}-GalCer has similar effects on NK T cells when administered to mice in vivo. Wild-type and CD1d-deficient mice on a C57BL/6 or mixed C57BL/6 x 129 background were therefore injected with 4 µg of {alpha}-GalCer; 18 h later mice were sacrificed and splenocytes were cultured in vitro for 72 h to measure proliferation, or alternatively, cultured for 60 h, after which IFN-{gamma} and IL-4 levels in these cultures were measured. Fig. 1GoA shows that {alpha}-GalCer but not vehicle induced strong proliferation of splenocytes and the production of significant amounts of both IFN-{gamma} and IL-4. These effects of {alpha}-GalCer were absent in CD1d-deficient mice that lack NK T cells (Fig. 1GoA). Administration of {alpha}-GalCer to mice also resulted in significant amounts of IFN-{gamma} in the serum of wild-type but not CD1d-deficient animals (Fig. 1GoB). Although serum IL-4 levels at this time point (18 h) were below the detection limit of the ELISA assay used (data not shown), significant IL-4 levels could be detected in the serum 2 h after {alpha}-GalCer injection (data not shown). RNase protection experiments further demonstrated that {alpha}-GalCer induced a variety of cytokines in the spleen of wild-type animals, including the typical Th1 cytokine IFN-{gamma} and the typical Th2 cytokines IL-4, IL-5, IL-6, IL-10, and IL-13 (Fig. 1GoD). Cytokine production by NK T cells in response to {alpha}-GalCer was accompanied by an increase in the expression of the early activation marker CD69 by these cells (Fig. 1GoC).



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FIGURE 1. Treatment of mice with {alpha}-GalCer results in production of Th1 and Th2 cytokines and polarizes NK T cells for the production of IL-4. A--D, Cytokine production upon in vivo treatment of mice with {alpha}-GalCer. Mice were injected with 4 µg of {alpha}-GalCer (in vehicle) or with vehicle only. Eighteen hours after treatment mice were sacrificed. Spleen cells from these animals were cultured in complete tissue culture medium for 72 h (without adding additional {alpha}-GalCer), and proliferation of responder cells was measured by [3H]thymidine incorporation, or alternatively, spleen cells were cultured for 60 h, after which IFN-{gamma} and IL-4 levels were determined in the culture supernatant by ELISA (A). Similarly, IFN-{gamma} levels in the serum were measured (B) and mRNA expression of the indicated cytokines in the spleen was measured by RNase protection assays (D). Autoradiographs for the cytokine bands were exposed for 2 days, whereas the signals for the mRNA controls (P32 and GDH) were exposed for 2 h. Expression of CD69 by NK T cells was measured by staining with anti-NK1.1-PE, anti-TCR-cychrome, and anti-CD69-FITC, followed by flow cytometry (C). Results shown represent expression levels of CD69 on NK1.1+TCR+ cells only. (E) Administration of {alpha}-GalCer to mice inhibits IFN-{gamma}- but not IL-4-producing NK T cells. CD1d+/+ or CD1d-/- mice were injected with {alpha}-GalCer or vehicle; 18 h or 9 days later, splenocytes from these mice were stimulated in vitro with 10 ng/ml of {alpha}-GalCer. IFN-{gamma} and IL-4 levels in the cultures were measured by ELISA. Results are shown for individual animals from one representative experiment of three separate experiments with two vehicle- and two {alpha}-GalCer-injected animals for the 18-h time point, and four vehicle- and four {alpha}-GalCer-injected animals for the 9-day time point.

 
Conventional T cells can differentiate into IFN-{gamma}-producing Th1 cells or IL-4-producing Th2 cells (19, 20). To test if NK T cells can be polarized to produce Th1 or Th2, cytokine patterns mice were immunized with {alpha}-GalCer and in vitro recall responses to this Ag were measured 18 h or 9 days later. Fig. 1GoE shows that 9 days after a single injection of {alpha}-GalCer NK T cells became polarized for the production of IL-4. These effects were specific to {alpha}-GalCer-injected mice (Fig. 1GoE), and dependent on CD1d, because CD1d-deficient mice never showed an in vitro response to {alpha}-GalCer, even when primed with this chemical before the assay (data not shown). These findings therefore indicated that immunization of mice with {alpha}-GalCer results in the generation of NK T cells that produce Th2 cytokines.

Administration of {alpha}-GalCer to mice results in the activation of conventional T cells, B cells, and NK cells

We sought out to test whether stimulation of NK T cells with {alpha}-GalCer can influence adaptive immune responses. First, we measured the activation status of conventional T cells, B cells and NK cells. Fig. 2GoA shows that as early as 18 h after administration of {alpha}-GalCer, the expression of the early activation marker CD69 was induced on mainstream T cells, B cells, and NK cells. This effect was not seen in CD1d knockout mice, indicating that these effects of {alpha}-GalCer are dependent on the activation of NK T cells. {alpha}-GalCer also induced expression of the costimulatory molecule CD86 on B cells, but did not induce expression of CD80 on these cells (Fig. 2GoB).



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FIGURE 2. Injection of {alpha}-GalCer into mice induces expression of the activation marker CD69 on mainstream T cells, B cells, and NK cells, and expression of the costimulatory molecule CD86 on B cells. Wild-type or CD1d knockout mice were injected with 4 µg of {alpha}-GalCer or with vehicle only, and 18 h later spleen cell suspensions were prepared. A, Expression of CD69 on TCR+ (T cells), B220+ (B cells), and NK1.1+TCR- (NK cells) cells was measured by flow cytometry. B, Expression of CD80 and CD86 on B220+ cells was measured by flow cytometry. One representative experiment of four is shown.

 
{alpha}-GalCer treatment promotes Th2 immune responses

A key factor in the differentiation of naive CD4+ T lymphocytes into functional effector T cells appears to be the cytokines that are present in the environment in which these cells develop (19, 20). IL-12 is a potent inducer of Th1 immune responses, whereas IL-4 promotes the development of Th2 immune responses. Our finding that {alpha}-GalCer polarizes NK T cells for the production of IL-4 suggested to us that this agent may promote Th2 responses. This possibility was also suggested by our observation that {alpha}-GalCer induces expression of the costimulatory molecule CD86 on B cells, because previous studies have shown that Ag presentation in the context of CD86 promotes Th2 development, whereas CD80 provides a more neutral differentiative signal (21, 22). To test this hypothesis, we measured IgE levels in the serum of {alpha}-GalCer-treated animals. Fig. 3GoA shows that as early as 6 days after administration of a single dose of {alpha}-GalCer, a dramatic increase in total serum IgE levels was observed. No significant differences were found in the serum levels of IgM, IgG1, and IgG2a (data not shown). Administration of {alpha}-GalCer to CD1d-deficient mice did not influence serum Ab isotype levels (data not shown).



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FIGURE 3. Treatment of mice with {alpha}-GalCer directs conventional T cells to the acquisition of a Th2 phenotype and production of IgE Abs. A, Effects of {alpha}-GalCer on serum IgE levels. Wild-type mice were injected with {alpha}-GalCer (4 µg/mouse) or vehicle. Mice were bled on days 0, 3, 6, and 9 after injection, and total serum IgE levels were measured by ELISA. Data are shown for individual mice from one representative experiment of four separate experiments with three vehicle- and three {alpha}-GalCer-injected animals. B and C, Administration of {alpha}-GalCer at the time of priming with protein Ag induces Ag-specific Th2 responses. Wild-type mice were injected with OVA (100 µg/mouse) together with {alpha}-GalCer (4 µg/mouse) or vehicle and emulsified in CFA. Eight days later mice were sacrificed and OVA-specific CD4+ T cell proliferation, cytokine production (B), and serum levels of OVA-specific Ab isotypes (C) were measured. Data are shown for individual mice from one representative experiment of four separate experiments with three vehicle- and three {alpha}-GalCer-injected animals.

 
To measure effects of {alpha}-GalCer on adaptive immune responses more directly, mice were immunized with the protein Ag OVA together with {alpha}-GalCer in an emulsion of CFA. Eight days later, Ag-specific CD4+ T cell responses and Ag-specific serum Ab levels were measured. Fig. 3GoB shows that OVA-specific T cells from {alpha}-GalCer-injected mice produced more IL-4 and less IFN-{gamma} than OVA-specific T cells from vehicle-injected mice, indicating that {alpha}-GalCer biased the response toward a Th2 phenotype. This conclusion was confirmed by the levels of OVA-specific Ig isotypes in the serum, which indicated a strong increase in OVA-specific IgE and a dramatic decrease in OVA-specific IgG2a Abs in the serum of {alpha}-GalCer-treated animals (Fig. 3GoC). Similar experiments with CD1d-deficient mice showed that absence of CD1d, by itself, had no effect on OVA-specific T and B cell responses, and that the effects of {alpha}-GalCer on T and B cell responses in wild-type mice were CD1d-dependent (data not shown). Collectively, these findings indicate that {alpha}-GalCer can direct the differentiation of naive T cell precursors toward the development of a Th2 phenotype.


    Discussion
 Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 
The discovery that NK T cells can produce large amounts of IL-4 quickly after stimulation (1, 2) lead many investigators to suggest that these cells may be critically important for the development of Th2 immune responses (11). However, experiments with ß2-microglobulin (12, 13, 14) and CD1d-deficient mice (8, 9, 10) subsequently showed that NK T cells are not absolutely required for the development of a Th2 response. In this report we demonstrated that treatment of mice with the glycolipid {alpha}-GalCer results in the activation of NK T cells and production by these cells of both IFN-{gamma} and IL-4, but that after this initial activation NK T cells become polarized cells that produce only IL-4. These changes in NK T cells were paralleled by profound effects on the adaptive immune response: 1) induction of the activation marker CD69 on mainstream T cells, B cells, and NK cells; 2) induction of the costimulatory molecule CD86 on B cells; and 3) an increase in serum IgE levels. Coadministration of {alpha}-GalCer and protein Ag in adjuvant promoted differentiation of naive Ag-specific CD4+ T cells into Th2 cells, which resulted in a profound increase in Ag-specific IgE Abs. Collectively, these findings demonstrate that {alpha}-GalCer can direct adaptive immune responses toward the Th2 pathway.

While our studies clearly demonstrated that {alpha}-GalCer polarized NK T cells for the production of IL-4, the mechanism by which this occurs remains unclear. One possibility would be that distinct populations of naive NK T cells produce Th1 and Th2 cytokines, and that {alpha}-GalCer selectively induces cell death in Th1 cytokine-producing NK T cells. An alternative possibility would be that naive NK T cells have the capacity to produce both Th1 and Th2 cytokines and that {alpha}-GalCer polarizes these cells for production of Th2 cytokines only. The latter scenario would closely resemble the differentiation program of conventional CD4+ T cells into Th2 cells. We are currently investigating the molecular and cellular mechanisms that are responsible for the polarized NK T cell responses induced by {alpha}-GalCer.

Polarized immune responses play an important role in the outcome of a variety of diseases, including infectious, allergic, and autoimmune diseases (19, 20). For example, resistance to most intracellular microorganisms, including bacteria, protozoa, and fungi, is linked to the induction of Th1 responses, whereas resistance to most extracellular microorganisms such as parasitic helminths is linked to the induction of Th2 responses. Our findings indicate that {alpha}-GalCer, when used as a vaccine adjuvant with sensitizing doses of Ag, can shift subsequent immune responses to a Th2 pattern. Such a strategy should prove useful for inclusion in vaccines directed against microorganisms where Th2 responses provide protection from disease.

Many inflammatory diseases, including organ-specific autoimmune diseases such as experimental allergic encephalomyelitis, insulin-dependent diabetes mellitus, and inflammatory bowel diseases, are characterized by pathogenic Th1 cells. Protection from these diseases can be achieved by switching the immune response from a Th1 pattern to a Th2 pattern, through immunomodulation with cytokines (19, 20). Immunomodulation with {alpha}-GalCer provides another, perhaps more attractive, way to inhibit the development of pathogenic Th1 cells in inflammatory immune responses. Indeed, we have recently demonstrated that repeated injection of {alpha}-GalCer into nonobese diabetic mice inhibits development of diabetes, and that this was associated with the production of Th2 cytokines by NK T cells (I. Serizawa, S. Hong, L. Wu, N. Singh, D. C. Scherer, T. Miura, T. Haba, A. C. Powers, Y. Koezuka, and L. Van Kaer, manuscript in preparation).

Another striking property of {alpha}-GalCer is its ability to stimulate both murine and human NK T cells (23, 24, 25). The remarkable conservation of this recognition system was further underscored by the observation that both mouse and human CD1d molecules were able to present {alpha}-GalCer to NK T cells from either species (23). Thus, our in vivo studies with {alpha}-GalCer in mice are directly relevant to human disease conditions. Therefore, this chemical may be useful for modulation of immune responses during prophylaxis and for prevention or therapeutic intervention of a variety of inflammatory diseases.


    Acknowledgments
 
We thank Drs. Barney Graham and Dean Ballard for providing various reagents, Jie Wie for technical assistance, David C. McFarland for help with flow cytometric analyses, and Dr. Takashi Nishimura for sharing information before publication.


    Footnotes
 
1 Current address: Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305. Back

2 Address correspondence and reprint requests to Dr. Luc Van Kaer, Howard Hughes Medical Institute, Department of Microbiology and Immunology, Vanderbilt University School of Medicine, 811 Rudolph Light Hall, Nashville, TN 37232. E-mail address: Back

3 Abbreviation used in this paper: {alpha}-GalCer, {alpha}-galactosylceramide. Back

Received for publication June 8, 1999. Accepted for publication July 6, 1999.


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 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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C. Hong, H. Lee, Y.-K. Park, J. Shin, S. Jung, H. Kim, S. Hong, and S.-H. Park
Regulation of Secondary Antigen-Specific CD8+ T-Cell Responses by Natural Killer T Cells
Cancer Res., May 15, 2009; 69(10): 4301 - 4308.
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BloodHome page
A. B. Pillai, T. I. George, S. Dutt, and S. Strober
Host natural killer T cells induce an interleukin-4-dependent expansion of donor CD4+CD25+Foxp3+ T regulatory cells that protects against graft-versus-host disease
Blood, April 30, 2009; 113(18): 4458 - 4467.
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G. Sireci, M. P. La Manna, D. Di Liberto, M. Lo Dico, M. Taniguchi, F. Dieli, and A. Salerno
Prophylaxis of lipopolysaccharide-induced shock by {alpha}-galactosylceramide
J. Leukoc. Biol., August 1, 2008; 84(2): 550 - 560.
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J. Leukoc. Biol.Home page
M. Biburger and G. Tiegs
Activation-induced NKT cell hyporesponsiveness protects from {alpha}-galactosylceramide hepatitis and is independent of active transregulatory factors
J. Leukoc. Biol., July 1, 2008; 84(1): 264 - 279.
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Am. J. Pathol.Home page
G. Chen, G. Han, J. Wang, R. Wang, R. Xu, B. Shen, J. Qian, and Y. Li
Induction of Active Tolerance and Involvement of CD1d-Restricted Natural Killer T Cells in Anti-CD3 F(ab')2 Treatment-Reversed New-Onset Diabetes in Nonobese Diabetic Mice
Am. J. Pathol., April 1, 2008; 172(4): 972 - 979.
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Cardiovasc ResHome page
L. Rogers, S. Burchat, J. Gage, M. Hasu, M. Thabet, L. Wilcox, T. A. Ramsamy, and S. C. Whitman
Deficiency of invariant V{alpha}14 natural killer T cells decreases atherosclerosis in LDL receptor null mice
Cardiovasc Res, April 1, 2008; 78(1): 167 - 174.
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J. Immunol.Home page
K. C. Roy, I. Maricic, A. Khurana, T. R. F. Smith, R. C. Halder, and V. Kumar
Involvement of Secretory and Endosomal Compartments in Presentation of an Exogenous Self-Glycolipid to Type II NKT Cells
J. Immunol., March 1, 2008; 180(5): 2942 - 2950.
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BloodHome page
G. A. Lang, T. S. Devera, and M. L. Lang
Requirement for CD1d expression by B cells to stimulate NKT cell-enhanced antibody production
Blood, February 15, 2008; 111(4): 2158 - 2162.
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Infect. Immun.Home page
J. H. F. Pedra, J. Mattner, J. Tao, S. M. Kerfoot, R. J. Davis, R. A. Flavell, P. W. Askenase, Z. Yin, and E. Fikrig
c-Jun NH2-Terminal Kinase 2 Inhibits Gamma Interferon Production during Anaplasma phagocytophilum Infection
Infect. Immun., January 1, 2008; 76(1): 308 - 316.
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J. Immunol.Home page
K. Coppieters, K. Van Beneden, P. Jacques, P. Dewint, A. Vervloet, B. Vander Cruyssen, S. Van Calenbergh, G. Chen, R. W. Franck, G. Verbruggen, et al.
A Single Early Activation of Invariant NK T Cells Confers Long-Term Protection against Collagen-Induced Arthritis in a Ligand-Specific Manner
J. Immunol., August 15, 2007; 179(4): 2300 - 2309.
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GutHome page
R H Grose, A G Cummins, and F M Thompson
Deficiency of invariant natural killer T cells in coeliac disease
Gut, June 1, 2007; 56(6): 790 - 795.
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Infect. Immun.Home page
T. Mallevaey, J. Fontaine, L. Breuilh, C. Paget, A. Castro-Keller, C. Vendeville, M. Capron, M. Leite-de-Moraes, F. Trottein, and C. Faveeuw
Invariant and Noninvariant Natural Killer T Cells Exert Opposite Regulatory Functions on the Immune Response during Murine Schistosomiasis
Infect. Immun., May 1, 2007; 75(5): 2171 - 2180.
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J. Immunol.Home page
C. Wiethe, M. Schiemann, D. Busch, L. Haeberle, M. Kopf, G. Schuler, and M. B. Lutz
Interdependency of MHC Class II/Self-Peptide and CD1d/Self-Glycolipid Presentation by TNF-Matured Dendritic Cells for Protection from Autoimmunity
J. Immunol., April 15, 2007; 178(8): 4908 - 4916.
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Rheumatology (Oxford)Home page
K. Coppieters, P. Dewint, K. Van Beneden, P. Jacques, S. Seeuws, G. Verbruggen, D. Deforce, and D. Elewaut
NKT cells: manipulable managers of joint inflammation
Rheumatology, April 1, 2007; 46(4): 565 - 571.
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Proc. Natl. Acad. Sci. USAHome page
G. Galli, P. Pittoni, E. Tonti, C. Malzone, Y. Uematsu, M. Tortoli, D. Maione, G. Volpini, O. Finco, S. Nuti, et al.
Invariant NKT cells sustain specific B cell responses and memory
PNAS, March 6, 2007; 104(10): 3984 - 3989.
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J. Leukoc. Biol.Home page
G. Sireci, M. P. La Manna, C. Di Sano, D. Di Liberto, S. A. Porcelli, M. Kronenberg, F. Dieli, and A. Salerno
Pivotal Advance: {alpha}-Galactosylceramide induces protection against lipopolysaccharide-induced shock
J. Leukoc. Biol., March 1, 2007; 81(3): 607 - 622.
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H. F. Rosenberg
The Shwartzman reaction repealed
J. Leukoc. Biol., March 1, 2007; 81(3): 623 - 624.
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J. Immunol.Home page
J. Novak, L. Beaudoin, S. Park, T. Griseri, L. Teyton, A. Bendelac, and A. Lehuen
Prevention of Type 1 Diabetes by Invariant NKT Cells Is Independent of Peripheral CD1d Expression
J. Immunol., February 1, 2007; 178(3): 1332 - 1340.
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J. Immunol.Home page
T. Iwai, Y. Tomita, S. Okano, I. Shimizu, Y. Yasunami, T. Kajiwara, Y. Yoshikai, M. Taniguchi, K. Nomoto, and H. Yasui
Regulatory Roles of NKT Cells in the Induction and Maintenance of Cyclophosphamide-Induced Tolerance
J. Immunol., December 15, 2006; 177(12): 8400 - 8409.
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G. Raghuraman, Y. Geng, and C.-R. Wang
IFN-beta-Mediated Up-Regulation of CD1d in Bacteria-Infected APCs
J. Immunol., December 1, 2006; 177(11): 7841 - 7848.
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J. Immunol.Home page
C. Hong, H. Lee, M. Oh, C.-Y. Kang, S. Hong, and S.-H. Park
CD4+ T Cells in the Absence of the CD8+ Cytotoxic T Cells Are Critical and Sufficient for NKT Cell-Dependent Tumor Rejection
J. Immunol., November 15, 2006; 177(10): 6747 - 6757.
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Infect. Immun.Home page
M. L. Lang and A. Glatman-Freedman
Do CD1-Restricted T Cells Contribute to Antibody-Mediated Immunity against Mycobacterium tuberculosis?
Infect. Immun., February 1, 2006; 74(2): 803 - 809.
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J. Immunol.Home page
M. I. Zimmer, A. Colmone, K. Felio, H. Xu, A. Ma, and C.-R. Wang
A Cell-Type Specific CD1d Expression Program Modulates Invariant NKT Cell Development and Function
J. Immunol., February 1, 2006; 176(3): 1421 - 1430.
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Int ImmunolHome page
S. Oki, C. Tomi, T. Yamamura, and S. Miyake
Preferential Th2 polarization by OCH is supported by incompetent NKT cell induction of CD40L and following production of inflammatory cytokines by bystander cells in vivo
Int. Immunol., December 1, 2005; 17(12): 1619 - 1629.
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S. Kojo, K.-i. Seino, M. Harada, H. Watarai, H. Wakao, T. Uchida, T. Nakayama, and M. Taniguchi
Induction of Regulatory Properties in Dendritic Cells by V{alpha}14 NKT Cells
J. Immunol., September 15, 2005; 175(6): 3648 - 3655.
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J. Immunol.Home page
S.-Y. Ko, H.-J. Ko, W.-S. Chang, S.-H. Park, M.-N. Kweon, and C.-Y. Kang
{alpha}-Galactosylceramide Can Act As a Nasal Vaccine Adjuvant Inducing Protective Immune Responses against Viral Infection and Tumor
J. Immunol., September 1, 2005; 175(5): 3309 - 3317.
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Int ImmunolHome page
T. Osada, M. A. Morse, H. K. Lyerly, and T. M. Clay
Ex vivo expanded human CD4+ regulatory NKT cells suppress expansion of tumor antigen-specific CTLs
Int. Immunol., September 1, 2005; 17(9): 1143 - 1155.
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BloodHome page
K. Minami, Y. Yanagawa, K. Iwabuchi, N. Shinohara, T. Harabayashi, K. Nonomura, and K. Onoe
Negative feedback regulation of T helper type 1 (Th1)/Th2 cytokine balance via dendritic cell and natural killer T cell interactions
Blood, September 1, 2005; 106(5): 1685 - 1693.
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C. Ronet, S. Darche, M. L. de Moraes, S. Miyake, T. Yamamura, J. A. Louis, L. H. Kasper, and D. Buzoni-Gatel
NKT Cells Are Critical for the Initiation of an Inflammatory Bowel Response against Toxoplasma gondii
J. Immunol., July 15, 2005; 175(2): 899 - 908.
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Y. Geng, P. Laslo, K. Barton, and C.-R. Wang
Transcriptional Regulation of CD1D1 by Ets Family Transcription Factors
J. Immunol., July 15, 2005; 175(2): 1022 - 1029.
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K. Haraguchi, T. Takahashi, A. Matsumoto, T. Asai, Y. Kanda, M. Kurokawa, S. Ogawa, H. Oda, M. Taniguchi, H. Hirai, et al.
Host-Residual Invariant NK T Cells Attenuate Graft-versus-Host Immunity
J. Immunol., July 15, 2005; 175(2): 1320 - 1328.
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Y. Ma, Q. Chen, and A. C. Ross
Retinoic Acid and Polyriboinosinic:Polyribocytidylic Acid Stimulate Robust Anti-Tetanus Antibody Production while Differentially Regulating Type 1/Type 2 Cytokines and Lymphocyte Populations
J. Immunol., June 15, 2005; 174(12): 7961 - 7969.
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J. S. Bezbradica, A. K. Stanic, N. Matsuki, H. Bour-Jordan, J. A. Bluestone, J. W. Thomas, D. Unutmaz, L. Van Kaer, and S. Joyce
Distinct Roles of Dendritic Cells and B Cells in Va14Ja18 Natural T Cell Activation In Vivo
J. Immunol., April 15, 2005; 174(8): 4696 - 4705.
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B. Chung, A. Aoukaty, J. Dutz, C. Terhorst, and R. Tan
Cutting Edge: Signaling Lymphocytic Activation Molecule-Associated Protein Controls NKT Cell Functions
J. Immunol., March 15, 2005; 174(6): 3153 - 3157.
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Arterioscler. Thromb. Vasc. Bio.Home page
A. M. Aslanian, H. A. Chapman, and I. F. Charo
Transient Role for CD1d-Restricted Natural Killer T Cells in the Formation of Atherosclerotic Lesions
Arterioscler Thromb Vasc Biol, March 1, 2005; 25(3): 628 - 632.
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Proc. Natl. Acad. Sci. USAHome page
D. Wu, G.-W. Xing, M. A. Poles, A. Horowitz, Y. Kinjo, B. Sullivan, V. Bodmer-Narkevitch, O. Plettenburg, M. Kronenberg, M. Tsuji, et al.
Bacterial glycolipids and analogs as antigens for CD1d-restricted NKT cells
PNAS, February 1, 2005; 102(5): 1351 - 1356.
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Cancer Res.Home page
Y. Suzuki, D. Wakita, K. Chamoto, Y. Narita, T. Tsuji, T. Takeshima, H. Gyobu, Y. Kawarada, S. Kondo, S. Akira, et al.
Liposome-Encapsulated CpG Oligodeoxynucleotides as a Potent Adjuvant for Inducing Type 1 Innate Immunity
Cancer Res., December 1, 2004; 64(23): 8754 - 8760.
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T. Crough, M. Nieda, and A. J. Nicol
Granulocyte Colony-Stimulating Factor Modulates {alpha}-Galactosylceramide-Responsive Human V{alpha}24+V{beta}11+ NKT Cells
J. Immunol., October 15, 2004; 173(8): 4960 - 4966.
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BloodHome page
Y. Nakai, K. Iwabuchi, S. Fujii, N. Ishimori, N. Dashtsoodol, K. Watano, T. Mishima, C. Iwabuchi, S. Tanaka, J. S. Bezbradica, et al.
Natural killer T cells accelerate atherogenesis in mice
Blood, October 1, 2004; 104(7): 2051 - 2059.
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V. V. Parekh, A. K. Singh, M. T. Wilson, D. Olivares-Villagomez, J. S. Bezbradica, H. Inazawa, H. Ehara, T. Sakai, I. Serizawa, L. Wu, et al.
Quantitative and Qualitative Differences in the In Vivo Response of NKT Cells to Distinct {alpha}- and {beta}-Anomeric Glycolipids
J. Immunol., September 15, 2004; 173(6): 3693 - 3706.
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L. Li, B. A. Sullivan, C. J. Aldrich, M. J. Soloski, J. Forman, A. G. Grandea III, P. E. Jensen, and L. Van Kaer
Differential Requirement for Tapasin in the Presentation of Leader- and Insulin-Derived Peptide Antigens to Qa-1b-Restricted CTLs
J. Immunol., September 15, 2004; 173(6): 3707 - 3715.
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Y. Nagayama, K. Watanabe, M. Niwa, S. M. McLachlan, and B. Rapoport
Schistosoma mansoni and {alpha}-Galactosylceramide: Prophylactic Effect of Th1 Immune Suppression in a Mouse Model of Graves' Hyperthyroidism
J. Immunol., August 1, 2004; 173(3): 2167 - 2173.
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T. Kimura, Y. Ishii, Y. Morishima, A. Shibuya, K. Shibuya, M. Taniguchi, M. Mochizuki, A. E. Hegab, T. Sakamoto, A. Nomura, et al.
Treatment with {alpha}-Galactosylceramide Attenuates the Development of Bleomycin-Induced Pulmonary Fibrosis
J. Immunol., May 1, 2004; 172(9): 5782 - 5789.
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Infect. Immun.Home page
S. Tawill, L. Le Goff, F. Ali, M. Blaxter, and J. E. Allen
Both Free-Living and Parasitic Nematodes Induce a Characteristic Th2 Response That Is Dependent on the Presence of Intact Glycans
Infect. Immun., January 1, 2004; 72(1): 398 - 407.
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Proc. Natl. Acad. Sci. USAHome page
J. Zhang, M. Dong, L. Li, Y. Fan, P. Pathre, J. Dong, D. Lou, J. M. Wells, D. Olivares-Villagomez, L. Van Kaer, et al.
Endonuclease G is required for early embryogenesis and normal apoptosis in mice
PNAS, December 23, 2003; 100(26): 15782 - 15787.
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Y. Yang, A. Ueno, M. Bao, Z. Wang, J. S. Im, S. Porcelli, and J.-W. Yoon
Control of NKT Cell Differentiation by Tissue-Specific Microenvironments
J. Immunol., December 1, 2003; 171(11): 5913 - 5920.
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I. F. Hermans, J. D. Silk, U. Gileadi, M. Salio, B. Mathew, G. Ritter, R. Schmidt, A. L. Harris, L. Old, and V. Cerundolo
NKT Cells Enhance CD4+ and CD8+ T Cell Responses to Soluble Antigen In Vivo through Direct Interaction with Dendritic Cells
J. Immunol., November 15, 2003; 171(10): 5140 - 5147.
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H. Xu, T. Chun, A. Colmone, H. Nguyen, and C.-R. Wang
Expression of CD1d Under the Control of a MHC Class Ia Promoter Skews the Development of NKT Cells, But Not CD8+ T Cells
J. Immunol., October 15, 2003; 171(8): 4105 - 4112.
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Infect. Immun.Home page
M. Skold and S. M. Behar
Role of CD1d-Restricted NKT Cells in Microbial Immunity
Infect. Immun., October 1, 2003; 71(10): 5447 - 5455.
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Proc. Natl. Acad. Sci. USAHome page
M. T. Wilson, C. Johansson, D. Olivares-Villagomez, A. K. Singh, A. K. Stanic, C.-R. Wang, S. Joyce, M. J. Wick, and L. Van Kaer
The response of natural killer T cells to glycolipid antigens is characterized by surface receptor down-modulation and expansion
PNAS, September 16, 2003; 100(19): 10913 - 10918.
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B. Johnston, C. H. Kim, D. Soler, M. Emoto, and E. C. Butcher
Differential Chemokine Responses and Homing Patterns of Murine TCR{alpha}{beta} NKT Cell Subsets
J. Immunol., September 15, 2003; 171(6): 2960 - 2969.
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M. Lisbonne, S. Diem, A. de Castro Keller, J. Lefort, L. M. Araujo, P. Hachem, J.-M. Fourneau, S. Sidobre, M. Kronenberg, M. Taniguchi, et al.
Cutting Edge: Invariant V{alpha}14 NKT Cells Are Required for Allergen-Induced Airway Inflammation and Hyperreactivity in an Experimental Asthma Model
J. Immunol., August 15, 2003; 171(4): 1637 - 1641.
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J.-Q. Yang, A. K. Singh, M. T. Wilson, M. Satoh, A. K. Stanic, J.-J. Park, S. Hong, S. D. Gadola, A. Mizutani, S. R. Kakumanu, et al.
Immunoregulatory Role of CD1d in the Hydrocarbon Oil-Induced Model of Lupus Nephritis
J. Immunol., August 15, 2003; 171(4): 2142 - 2153.
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Proc. Natl. Acad. Sci. USAHome page
S. Gillessen, Y. N. Naumov, E. E. S. Nieuwenhuis, M. A. Exley, F. S. Lee, N. Mach, A. D. Luster, R. S. Blumberg, M. Taniguchi, S. P. Balk, et al.
CD1d-restricted T cells regulate dendritic cell function and antitumor immunity in a granulocyte-macrophage colony-stimulating factor-dependent fashion
PNAS, July 22, 2003; 100(15): 8874 - 8879.
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JEMHome page
S.-i. Fujii, K. Shimizu, C. Smith, L. Bonifaz, and R. M. Steinman
Activation of Natural Killer T Cells by {alpha}-Galactosylceramide Rapidly Induces the Full Maturation of Dendritic Cells In Vivo and Thereby Acts as an Adjuvant for Combined CD4 and CD8 T Cell Immunity to a Coadministered Protein
J. Exp. Med., July 21, 2003; 198(2): 267 - 279.
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J. Virol.Home page
A. Motsinger, A. Azimzadeh, A. K. Stanic, R. P. Johnson, L. Van Kaer, S. Joyce, and D. Unutmaz
Identification and Simian Immunodeficiency Virus Infection of CD1d-Restricted Macaque Natural Killer T Cells
J. Virol., July 15, 2003; 77(14): 8153 - 8158.
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Proc. Natl. Acad. Sci. USAHome page
J. L. Matsuda, L. Gapin, J. L. Baron, S. Sidobre, D. B. Stetson, M. Mohrs, R. M. Locksley, and M. Kronenberg
Mouse V{alpha}14i natural killer T cells are resistant to cytokine polarization in vivo
PNAS, July 8, 2003; 100(14): 8395 - 8400.
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N. Matsuki, A. K. Stanic, M. E. Embers, L. Van Kaer, L. Morel, and S. Joyce
Genetic Dissection of V{alpha}14J{alpha}18 Natural T Cell Number and Function in Autoimmune-Prone Mice
J. Immunol., June 1, 2003; 170(11): 5429 - 5437.
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G. Zhang, R. D. Nichols, M. Taniguchi, T. Nakayama, and M. J. Parmely
Gamma Interferon Production by Hepatic NK T Cells during Escherichia coli Infection Is Resistant to the Inhibitory Effects of Oxidative Stress
Infect. Immun., May 1, 2003; 71(5): 2468 - 2477.
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R. R. Singh, V. Saxena, S. Zang, L. Li, F. D. Finkelman, D. P. Witte, and C. O. Jacob
Differential Contribution of IL-4 and STAT6 vs STAT4 to the Development of Lupus Nephritis
J. Immunol., May 1, 2003; 170(9): 4818 - 4825.
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T. Yoshimoto, B. Min, T. Sugimoto, N. Hayashi, Y. Ishikawa, Y. Sasaki, H. Hata, K. Takeda, K. Okumura, L. Van Kaer, et al.
Nonredundant Roles for CD1d-restricted Natural Killer T Cells and Conventional CD4+ T Cells in the Induction of Immunoglobulin E Antibodies in Response to Interleukin 18 Treatment of Mice
J. Exp. Med., April 21, 2003; 197(8): 997 - 1005.
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G. Galli, S. Nuti, S. Tavarini, L. Galli-Stampino, C. De Lalla, G. Casorati, P. Dellabona, and S. Abrignani
CD1d-restricted Help To B Cells By Human Invariant Natural Killer T Lymphocytes
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S. Huber, D. Sartini, and M. Exley
Role of CD1d in Coxsackievirus B3-Induced Myocarditis
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K. Kuwata, H. Watanabe, S.-Y. Jiang, T. Yamamoto, C. Tomiyama-Miyaji, T. Abo, T. Miyazaki, and M. Naito
AIM Inhibits Apoptosis of T Cells and NKT Cells in Corynebacterium-Induced Granuloma Formation in Mice
Am. J. Pathol., March 1, 2003; 162(3): 837 - 847.
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D. Stober, I. Jomantaite, R. Schirmbeck, and J. Reimann
NKT Cells Provide Help for Dendritic Cell-Dependent Priming of MHC Class I-Restricted CD8+ T Cells In Vivo
J. Immunol., March 1, 2003; 170(5): 2540 - 2548.
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Proc. Natl. Acad. Sci. USAHome page
A. K. Stanic, A. D. De Silva, J.-J. Park, V. Sriram, S. Ichikawa, Y. Hirabyashi, K. Hayakawa, L. Van Kaer, R. R. Brutkiewicz, and S. Joyce
Defective presentation of the CD1d1-restricted natural Va14Ja18 NKT lymphocyte antigen caused by beta -D-glucosylceramide synthase deficiency
PNAS, February 18, 2003; 100(4): 1849 - 1854.
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S. L. H. van Dommelen, H. A. Tabarias, M. J. Smyth, and M. A. Degli-Esposti
Activation of Natural Killer (NK) T Cells during Murine Cytomegalovirus Infection Enhances the Antiviral Response Mediated by NK Cells
J. Virol., February 1, 2003; 77(3): 1877 - 1884.
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E. E. S. Nieuwenhuis, M. F. Neurath, N. Corazza, H. Iijima, J. Trgovcich, S. Wirtz, J. Glickman, D. Bailey, M. Yoshida, P. R. Galle, et al.
Disruption of T helper 2-immune responses in Epstein-Barr virus-induced gene 3-deficient mice
PNAS, December 24, 2002; 99(26): 16951 - 16956.
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Infect. Immun.Home page
A. Chackerian, J. Alt, V. Perera, and S. M. Behar
Activation of NKT Cells Protects Mice from Tuberculosis
Infect. Immun., November 1, 2002; 70(11): 6302 - 6309.
[Abstract] [Full Text] [PDF]


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Infect. Immun.Home page
A. Metwali, A. Blum, D. E. Elliott, and J. V. Weinstock
Interleukin-4 Receptor {alpha} Chain and STAT6 Signaling Inhibit Gamma Interferon but Not Th2 Cytokine Expression within Schistosome Granulomas
Infect. Immun., October 1, 2002; 70(10): 5651 - 5658.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
C. Faveeuw, V. Angeli, J. Fontaine, C. Maliszewski, A. Capron, L. Van Kaer, M. Moser, M. Capron, and F. Trottein
Antigen Presentation by CD1d Contributes to the Amplification of Th2 Responses to Schistosoma mansoni Glycoconjugates in Mice
J. Immunol., July 15, 2002; 169(2): 906 - 912.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
L. T. Mars, V. Laloux, K. Goude, S. Desbois, A. Saoudi, L. Van Kaer, H. Lassmann, A. Herbelin, A. Lehuen, and R. S. Liblau
Cutting Edge: V{alpha}14-J{alpha}281 NKT Cells Naturally Regulate Experimental Autoimmune Encephalomyelitis in Nonobese Diabetic Mice
J. Immunol., June 15, 2002; 168(12): 6007 - 6011.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
T. J. Roberts, V. Sriram, P. M. Spence, M. Gui, K. Hayakawa, I. Bacik, J. R. Bennink, J. W. Yewdell, and R. R. Brutkiewicz
Recycling CD1d1 Molecules Present Endogenous Antigens Processed in an Endocytic Compartment to NKT Cells
J. Immunol., June 1, 2002; 168(11): 5409 - 5414.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
M. S. Duthie and S. J. Kahn
Treatment with {alpha}-Galactosylceramide Before Trypanosoma cruzi Infection Provides Protection or Induces Failure to Thrive
J. Immunol., June 1, 2002; 168(11): 5778 - 5785.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
A. L. Marzo, V. Vezys, K. Williams, D. F. Tough, and L. Lefrancois
Tissue-Level Regulation of Th1 and Th2 Primary and Memory CD4 T Cells in Response to Listeria Infection
J. Immunol., May 1, 2002; 168(9): 4504 - 4510.
[Abstract] [Full Text] [PDF]


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Infect. Immun.Home page
P. Balmer and E. Devaney
NK T Cells Are a Source of Early Interleukin-4 following Infection with Third-Stage Larvae of the Filarial Nematode Brugia pahangi
Infect. Immun., April 1, 2002; 70(4): 2215 - 2219.
[Abstract] [Full Text] [PDF]


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J. Virol.Home page
T. R. Johnson, S. Hong, L. Van Kaer, Y. Koezuka, and B. S. Graham
NK T Cells Contribute to Expansion of CD8+ T Cells and Amplification of Antiviral Immune Responses to Respiratory Syncytial Virus
J. Virol., March 27, 2002; 76(9): 4294 - 4303.
[Abstract] [Full Text] [PDF]


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JEMHome page
G. Gonzalez-Aseguinolaza, L. Van Kaer, C. C. Bergmann, J. M. Wilson, J. Schmieg, M. Kronenberg, T. Nakayama, M. Taniguchi, Y. Koezuka, and M. Tsuji
Natural Killer T Cell Ligand {alpha}-Galactosylceramide Enhances Protective Immunity Induced by Malaria Vaccines
J. Exp. Med., March 4, 2002; 195(5): 617 - 624.
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JEMHome page
J. E. Gumperz, S. Miyake, T. Yamamura, and M. B. Brenner
Functionally Distinct Subsets of CD1d-restricted Natural Killer T Cells Revealed by CD1d Tetramer Staining
J. Exp. Med., March 4, 2002; 195(5): 625 - 636.
[Abstract] [Full Text] [PDF]


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JEMHome page
A. Bendelac and R. Medzhitov
Adjuvants of Immunity: Harnessing Innate Immunity to Promote Adaptive Immunity
J. Exp. Med., March 4, 2002; 195(5): F19 - F23.
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BloodHome page
M. J. Smyth, N. Y. Crowe, D. G. Pellicci, K. Kyparissoudis, J. M. Kelly, K. Takeda, H. Yagita, and D. I. Godfrey
Sequential production of interferon-gamma by NK1.1+ T cells and natural killer cells is essential for the antimetastatic effect of alpha -galactosylceramide
Blood, February 15, 2002; 99(4): 1259 - 1266.
[Abstract] [Full Text] [PDF]


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JEMHome page
A. W. Jahng, I. Maricic, B. Pedersen, N. Burdin, O. Naidenko, M. Kronenberg, Y. Koezuka, and V. Kumar
Activation of Natural Killer T Cells Potentiates or Prevents Experimental Autoimmune Encephalomyelitis
J. Exp. Med., December 17, 2001; 194(12): 1789 - 1799.
[Abstract] [Full Text] [PDF]


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JEMHome page
A. K. Singh, M. T. Wilson, S. Hong, D. Olivares-Villagomez, C. Du, A. K. Stanic, S. Joyce, S. Sriram, Y. Koezuka, and L. Van Kaer
Natural Killer T Cell Activation Protects Mice Against Experimental Autoimmune Encephalomyelitis
J. Exp. Med., December 17, 2001; 194(12): 1801 - 1811.
[Abstract] [Full Text] [PDF]


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DiabetesHome page
Y. Yang, M. Bao, and J.-W. Yoon
Intrinsic Defects in the T-Cell Lineage Results in Natural Killer T-Cell Deficiency and the Development of Diabetes in the Nonobese Diabetic Mouse
Diabetes, December 1, 2001; 50(12): 2691 - 2699.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
K. Kawakami, Y. Kinjo, K. Uezu, S. Yara, K. Miyagi, Y. Koguchi, T. Nakayama, M. Taniguchi, and A. Saito
Monocyte Chemoattractant Protein-1-Dependent Increase of V{alpha}14 NKT Cells in Lungs and Their Roles in Th1 Response and Host Defense in Cryptococcal Infection
J. Immunol., December 1, 2001; 167(11): 6525 - 6532.
[Abstract] [Full Text] [PDF]


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Infect. Immun.Home page
K. Kawakami, Y. Kinjo, S. Yara, K. Uezu, Y. Koguchi, M. Tohyama, M. Azuma, K. Takeda, S. Akira, and A. Saito
Enhanced Gamma Interferon Production through Activation of Valpha 14+ Natural Killer T Cells by alpha -Galactosylceramide in Interleukin-18-Deficient Mice with Systemic Cryptococcosis
Infect. Immun., November 1, 2001; 69(11): 6643 - 6650.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
S. Muhammad Ali Tahir, O. Cheng, A. Shaulov, Y. Koezuka, G. J. Bubley, S. B. Wilson, S. P. Balk, and M. A. Exley
Loss of IFN-{gamma} Production by Invariant NK T Cells in Advanced Cancer
J. Immunol., October 1, 2001; 167(7): 4046 - 4050.
[Abstract] [Full Text] [PDF]


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JEMHome page
B. Wang, Y.-B. Geng, and C.-R. Wang
Cd1-Restricted Nk T Cells Protect Nonobese Diabetic Mice from Developing Diabetes
J. Exp. Med., August 6, 2001; 194(3): 313 - 320.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
Z. Trobonjaca, F. Leithauser, P. Moller, R. Schirmbeck, and J. Reimann
Activating Immunity in the Liver. I. Liver Dendritic Cells (but Not Hepatocytes) Are Potent Activators of IFN-{gamma} Release by Liver NKT Cells
J. Immunol., August 1, 2001; 167(3): 1413 - 1422.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
Y. Hayakawa, K. Takeda, H. Yagita, L. Van Kaer, I. Saiki, and K. Okumura
Differential Regulation of Th1 and Th2 Functions of NKT Cells by CD28 and CD40 Costimulatory Pathways
J. Immunol., May 15, 2001; 166(10): 6012 - 6018.
[Abstract] [Full Text] [PDF]


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J. Leukoc. Biol.Home page
M. A. Exley, N. J. Bigley, O. Cheng, S. M. A. Tahir, S. T. Smiley, Q. L. Carter, H. F. Stills, M. J. Grusby, Y. Koezuka, M. Taniguchi, et al.
CD1d-reactive T-cell activation leads to amelioration of disease caused by diabetogenic encephalomyocarditis virus
J. Leukoc. Biol., May 1, 2001; 69(5): 713 - 718.
[Abstract] [Full Text]


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J. Immunol.Home page
V. Laloux, L. Beaudoin, D. Jeske, C. Carnaud, and A. Lehuen
NK T Cell-Induced Protection Against Diabetes in V{{alpha}}14-J{{alpha}}281 Transgenic Nonobese Diabetic Mice Is Associated with a Th2 Shift Circumscribed Regionally to the Islets and Functionally to Islet Autoantigen
J. Immunol., March 15, 2001; 166(6): 3749 - 3756.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
Z. Trobonjaca, F. Leithauser, P. Moller, H. Bluethmann, Y. Koezuka, H. R. MacDonald, and J. Reimann
MHC-II-Independent CD4+ T Cells Induce Colitis in Immunodeficient RAG-/- Hosts
J. Immunol., March 15, 2001; 166(6): 3804 - 3812.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
B. Wang, T. Chun, I. C. Rulifson, M. Exley, S. P. Balk, and C.-R. Wang
Human CD1d Functions as a Transplantation Antigen and a Restriction Element in Mice
J. Immunol., March 15, 2001; 166(6): 3829 - 3836.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
A. Karadimitris, S. Gadola, M. Altamirano, D. Brown, A. Woolfson, P. Klenerman, J.-L. Chen, Y. Koezuka, I. A. G. Roberts, D. A. Price, et al.
From the Cover: Human CD1d-glycolipid tetramers generated by in vitro oxidative refolding chromatography
PNAS, March 13, 2001; 98(6): 3294 - 3298.
[Abstract] [Full Text] [PDF]


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J. Immunol.Home page
M. C. Leite-de-Moraes, A. Hameg, M. Pacilio, Y. Koezuka, M. Taniguchi, L. Van Kaer, E. Schneider, M. Dy, and A. Herbelin
IL-18 Enhances IL-4 Production by Ligand-Activated NKT Lymphocytes: A Pro-Th2 Effect of IL-18 Exerted Through NKT Cells
J. Immunol., January 15, 2001; 166(2): 945 - 951.
[Abstract] [Full Text] [PDF]


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