Online citations, reference lists, and bibliographies.
← Back to Search

Natural Killer T Cell Activation Protects Mice Against Experimental Autoimmune Encephalomyelitis

A. Singh, M. Wilson, Seokmann Hong, D. Olivares-Villagómez, C. Du, A. K. Stanic, S. Joyce, S. Sriram, Y. Koezuka, L. Van Kaer
Published 2001 · Biology, Medicine

Save to my Library
Download PDF
Analyze on Scholarcy Visualize in Litmaps
Share
Reduce the time it takes to create your bibliography by a factor of 10 by using the world’s favourite reference manager
Time to take this seriously.
Get Citationsy
Experimental autoimmune encephalomyelitis (EAE) serves as a prototypic model for T cell–mediated autoimmunity. Vα14 natural killer T (NKT) cells are a subset of T lymphocytes that recognize glycolipid antigens presented by the nonpolymorphic major histocompatibility complex (MHC) class I–like protein CD1d. Here, we show that activation of Vα14 NKT cells by the glycosphingolipid α-galactosylceramide (α-GalCer) protects susceptible mice against EAE. β-GalCer, which binds CD1d but is not recognized by NKT cells, failed to protect mice against EAE. Furthermore, α-GalCer was unable to protect CD1d knockout (KO) mice against EAE, indicating the requirement for an intact CD1d antigen presentation pathway. Protection of disease conferred by α-GalCer correlated with its ability to suppress myelin antigen-specific Th1 responses and/or to promote myelin antigen-specific Th2 cell responses. α-GalCer was unable to protect IL-4 KO and IL-10 KO mice against EAE, indicating a critical role for both of these cytokines. Because recognition of α-GalCer by NKT cells is phylogenetically conserved, our findings have identified NKT cells as novel target cells for treatment of inflammatory diseases of the central nervous system.
This paper references
10.1084/JEM.169.4.1199
Site-restricted persistent cytomegalovirus infection after selective long-term depletion of CD4+ T lymphocytes
S. Jonjić (1989)
10.1093/INTIMM/2.6.539
Lymphotoxin and tumor necrosis factor-alpha production by myelin basic protein-specific T cell clones correlates with encephalitogenicity.
M. Powell (1990)
10.1126/science.256.5060.1210
Less Mortality but More Relapses in Experimental Allergic Encephalomyelitis in CD8-/- Mice
D. Koh (1992)
10.1126/science.256.5060.1213
Role of CD8+ T Cells in Murine Experimental Allergic Encephalomyelitis
Hong Jiang (1992)
10.1073/PNAS.89.1.421
Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor beta after antigen-specific triggering.
A. Miller (1992)
10.1084/JEM.176.5.1355
Oral tolerance to myelin basic protein and natural recovery from experimental autoimmune encephalomyelitis are associated with downregulation of inflammatory cytokines and differential upregulation of transforming growth factor beta, interleukin 4, and prostaglandin E expression in the brain
S. Khoury (1992)
10.1016/S0040-4039(00)73889-5
Agelasphins, novel α-galactosylceramides from the marine sponge Agelas mauritianus
T. Natori (1993)
Agelasphins, novel ␣-galactosylceramides from the marine sponge Agelas Ligand-activated NKT Cells Protect Mice against EAE Mauritianus
T Natori (1993)
Agelasphins, novel -galactosylceramides from the marine sponge Agelas 1810 Ligand-activated NKT Cells Protect Mice against EAE Mauritianus
T. Natori (1993)
10.1073/PNAS.92.25.11931
Defective IgE production by SJL mice is linked to the absence of CD4+, NK1.1+ T cells that promptly produce interleukin 4.
T. Yoshimoto (1995)
10.1084/JEM.182.4.1163
Selective reduction of T cells bearing invariant V alpha 24J alpha Q antigen receptor in patients with systemic sclerosis
T. Sumida (1995)
10.1021/JM00012A018
Structure-activity relationship of alpha-galactosylceramides against B16-bearing mice.
M. Morita (1995)
10.1016/0165-5728(95)00100-G
Cytokine production in the central nervous system of Lewis rats with experimental autoimmune encephalomyelitis: dynamics of mRNA expression for interleukin-10, interleukin-12, cytolysin, tumor necrosis factor α and tumor necrosis factor β
S. Issazadeh (1995)
Selective reduction of T cells bearing invariant V␣24J␣Q antigen receptor in patients with systemic sclerosis
T Sumida (1995)
Selective reduction of T cells bearing invariant V 24J Q antigen receptor in patients with systemic sclerosis
T. Sumida (1995)
10.1002/EJI.1830261226
Early quantitative and functional deficiency of NK1+‐like thymocytes in the NOD mouse
J. Gombert (1996)
10.1084/JEM.184.6.2271
Experimental Autoimmune Encephalomyelitis Induction in Genetically B Cell–deficient Mice
S. Wolf (1996)
Selective reduction of V alpha 14+ NK T cells associated with disease development in autoimmune-prone mice.
M. Mieza (1996)
10.1126/SCIENCE.278.5343.1626
CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides.
T. Kawano (1997)
10.1016/S1074-7613(00)80289-7
Impaired NK1+ T cell development and early IL-4 production in CD1-deficient mice.
Y. Chen (1997)
10.1126/SCIENCE.275.5302.977
Immunoglobulin E Production in the Absence of Interleukin-4-Secreting CD1-Dependent Cells
S. Smiley (1997)
10.1016/S1074-7613(00)80290-3
CD1d1 mutant mice are deficient in natural T cells that promptly produce IL-4.
S. K. Mendiratta (1997)
10.1146/ANNUREV.IMMUNOL.15.1.535
Mouse CD1-specific NK1 T cells: development, specificity, and function.
A. Bendelac (1997)
10.1084/JEM.186.1.109
Requirements for CD1d Recognition by Human Invariant Vα24+ CD4−CD8− T Cells
M. Exley (1997)
10.2337/diab.46.4.572
Association Between αβTCR+CD4−CD8− T-Cell Deficiency and IDDM in NOD/Lt Mice
A. Baxter (1997)
10.1016/S0165-5728(98)91292-9
Prevention of experimental allergic encephalomyelitis via inhibition of IL-12 signaling and IL-1-mediated Th1 differentiation; an effect of the novel anti-inflammatory drug lisofylline
S. Sriram (1998)
Selective Ability of Mouse CD1 to Present Glycolipids: α-Galactosylceramide Specifically Stimulates Vα14 + NK T Lymphocytes
N. Burdin (1998)
10.1016/S0165-5728(98)91696-4
Regulation of Experimental Autoimmune Encephalomyelitis by Natural Killer (NK) Cells
Ben-ning Zhang (1998)
Differential expression of inflammatory cytokines parallels progression of central nervous system pathology in two clinically distinct models of multiple sclerosis.
W. Begolka (1998)
10.1084/JEM.188.10.1875
CD4+ T Cells Prevent Spontaneous Experimental Autoimmune Encephalomyelitis in Anti–Myelin Basic Protein T Cell Receptor Transgenic Mice
F. Van de Keere (1998)
10.1084/JEM.188.8.1521
CD1d-mediated Recognition of an α-Galactosylceramide by Natural Killer T Cells Is Highly Conserved through Mammalian Evolution
L. Brossay (1998)
10.1038/34419
Extreme Th1 bias of invariant Vα24JαQ T cells in type 1 diabetes
S. Wilson (1998)
10.1084/JEM.188.8.1529
CD1d-restricted Recognition of Synthetic Glycolipid Antigens by Human Natural Killer T Cells
F. M. Spada (1998)
Kinetics of expression of costimulatory molecules and their ligands in murine relapsing experimental autoimmune encephalomyelitis in vivo.
S. Issazadeh (1998)
10.1084/JEM.188.10.1883
Regulatory CD4+ T Cells Expressing Endogenous T Cell Receptor Chains Protect Myelin Basic Protein–specific Transgenic Mice from Spontaneous Autoimmune Encephalomyelitis
Danyvid Olivares-Villagómez (1998)
CD1drestricted recognition of synthetic glycolipid antigens by human natural killer T cells
F. M. Spada (1998)
IL-7 up-regulates IL-4 production by splenic NK1.1+ and NK1.1- MHC class I-like/CD1-dependent CD4+ T cells.
A. Hameg (1999)
10.1084/JEM.189.7.1121
The Natural Killer T (NKT) Cell Ligand α-Galactosylceramide Demonstrates Its Immunopotentiating Effect by Inducing Interleukin (IL)-12 Production by Dendritic Cells and IL-12 Receptor Expression on NKT Cells
H. Kitamura (1999)
10.1111/j.1600-065X.1999.tb01304.x
Lipid antigen presentation in the immune system; lessons learned from CD 1 d knockout mice
Seokmann Hong (1999)
10.1084/JEM.190.7.963
A Defect in Interleukin 12–Induced Activation and Interferon γ Secretion of Peripheral Natural Killer T Cells in Nonobese Diabetic Mice Suggests New Pathogenic Mechanisms for Insulin-Dependent Diabetes Mellitus
M. Falcone (1999)
10.1084/JEM.190.9.1197
Immune privilege: keeping an eye on natural killer T cells.
Seokmann Hong (1999)
10.1007/978-3-662-09709-0_5
Redirecting Th1 and Th2 responses in autoimmune disease.
C. Pearson (1999)
10.1016/S0198-8859(98)00100-1
Activation of human Vα24NKT cells by α-glycosylceramide in a CD1d-restricted and Vα24TCR-mediated manner
M. Nieda (1999)
10.1016/S0896-6273(00)81107-1
Assessment of Animal Models for MS and Demyelinating Disease in the Design of Rational Therapy
L Steinman (1999)
Cutting edge: Cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells.
C. Carnaud (1999)
10.1002/(SICI)1521-4141(199906)29:06<2014::AID-IMMU2014>3.0.CO;2-G
Immunization with α‐galactosylceramide polarizes CD1‐reactive NK T cells towards Th2 cytokine synthesis
N. Burdin (1999)
10.1084/JEM.190.9.1215
Cd1-Reactive Natural Killer T Cells Are Required for Development of Systemic Tolerance through an Immune-Privileged Site
K. Sonoda (1999)
Cutting edge: activation of NK T cells by CD1d and alpha-galactosylceramide directs conventional T cells to the acquisition of a Th2 phenotype.
N. Singh (1999)
Activation of human V 24 NKT cells by -glycosylceramide in a CD1d-restricted and V 24 TCR-mediated
M. Nieda (1999)
10.4049/jimmunol.165.9.4797
Cutting Edge: CD1d Deficiency Impairs Murine Host Defense Against the Spirochete, Borrelia burgdorferi1
H. Kumar (2000)
10.1084/JEM.191.11.1895
In Vivo Identification of Glycolipid Antigen–Specific T Cells Using Fluorescent Cd1d Tetramers
K. Benlagha (2000)
CD4[+] Vα14 natural killer T cells are essential for acceptance of rat islet xenografts in mice
池原 康人 (2000)
10.4049/jimmunol.164.8.4375
Differential Expression of NK T Cell Vα24JαQ Invariant TCR Chain in the Lesions of Multiple Sclerosis and Chronic Inflammatory Demyelinating Polyneuropathy1
Z. Illés (2000)
10.1084/JEM.191.4.661
Differential Tumor Surveillance by Natural Killer (Nk) and Nkt Cells
M. Smyth (2000)
10.1016/S1074-7613(00)80174-0
Murine CD1d-restricted T cell recognition of cellular lipids.
J. Gumperz (2000)
10.1084/JEM.192.5.741
Tracking the Response of Natural Killer T Cells to a Glycolipid Antigen Using Cd1d Tetramers
J. Matsuda (2000)
10.1093/INTIMM/12.9.1267
CD4(+) v(alpha)14 NKT cells play a crucial role in an early stage of protective immunity against infection with Leishmania major.
H. Ishikawa (2000)
10.1002/(SICI)1521-4141(200004)30:4<985::AID-IMMU985>3.0.CO;2-E
Selective induction of NK cell proliferation and cytotoxicity by activated NKT cells
G. Eberl (2000)
10.1038/82771
NKT cell–mediated repression of tumor immunosurveillance by IL-13 and the IL-4R–STAT6 pathway
M. Terabe (2000)
10.1006/CIMM.1999.1602
alpha-galactosylceramide induces early B-cell activation through IL-4 production by NKT cells.
H. Kitamura (2000)
10.1038/82782
Immune suppression and skin cancer development: regulation by NKT cells
A. Moodycliffe (2000)
10.1053/GAST.2000.9114
Activation of natural killer T cells by alpha-galactosylceramide in the presence of CD1d provides protection against colitis in mice.
L. Saubermann (2000)
10.1002/1521-4141(200007)30:7<1919::AID-IMMU1919>3.0.CO;2-3
Activation of hepatic NKT cells and subsequent liver injury following administration of α‐galactosylceramide
Y. Osman (2000)
10.4049/jimmunol.165.8.4305
Selective Bystander Proliferation of Memory CD4+ and CD8+ T Cells Upon NK T or T Cell Activation
G. Eberl (2000)
10.11501/3166116
CD1d-restricted and TCR-mediated activation of V α14 NKT cells by glycosylceramides
河野 鉄 (2000)
10.1016/S0167-5699(00)01735-7
NKT cells: facts, functions and fallacies.
D. Godfrey (2000)
10.1172/JCI8922
CD4(+) Valpha14 natural killer T cells are essential for acceptance of rat islet xenografts in mice.
Y. Ikehara (2000)
NKT cells: facts, functions and falla 1809
D. I. Godfrey (2000)
NKT cells: facts, functions and falla on Jne
D. I. Godfrey (2000)
KRN7000, an NKT cell enhancer, in 1811 Singh et al. patients with solid tumors - a phase I study of the EORTC BTDG
G. Giaccone (2000)
KRN7000, an NKT cell enhancer, in patients with solid tumors -a phase I study of the EORTC BTDG
G Giaccone (2000)
KRN7000, an NKT cell enhancer, in on Jne
G. Giaccone (2000)
10.1038/84603
Genetic models for CNS inflammation
T. Owens (2001)
10.4049/jimmunol.167.3.1164
CD1d-Restricted NKT Cells: An Interstrain Comparison1
Kirsten J. L. Hammond (2001)
10.1038/35097097
A synthetic glycolipid prevents autoimmune encephalomyelitis by inducing TH2 bias of natural killer T cells
K. Miyamoto (2001)
10.4049/jimmunol.166.2.945
IL-18 Enhances IL-4 Production by Ligand-Activated NKT Lymphocytes: A Pro-Th2 Effect of IL-18 Exerted Through NKT Cells1
M. Leite-de-Moraes (2001)
10.4049/jimmunol.166.10.6012
Differential Regulation of Th1 and Th2 Functions of NKT Cells by CD28 and CD40 Costimulatory Pathways1
Y. Hayakawa (2001)
10.1073/pnas.041608298
Requirement for natural killer T (NKT) cells in the induction of allograft tolerance
K. Seino (2001)
10.1006/CLIM.2000.4942
Decreases in Interleukin-4 Secretion by Invariant CD4−CD8−Vα24JαQ T Cells in Peripheral Blood of Patients with Relapsing–Remitting Multiple Sclerosis
R. Gausling (2001)
10.1038/nm0901-1057
Activation of natural killer T cells by α-galactosylceramide treatment prevents the onset and recurrence of autoimmune Type 1 diabetes
S. Sharif (2001)
10.1189/jlb.69.5.713
CD1d‐reactive T‐cell activation leads to amelioration of disease caused by diabetogenic encephalomyocarditis virus
M. Exley (2001)
10.1038/nm0901-1052
The natural killer T-cell ligand α-galactosylceramide prevents autoimmune diabetes in non-obese diabetic mice
Seokmann Hong (2001)
10.1007/PL00000869
CD1d and natural T cells: how their properties jump-start the immune system
S. Joyce (2001)
10.1002/1529-0131(200105)44:5<1127::AID-ANR194>3.0.CO;2-W
Dysfunction of T cell receptor AV24AJ18+, BV11+ double-negative regulatory natural killer T cells in autoimmune diseases.
S. Kojo (2001)
10.1006/CLIM.2001.5060
Circulating Vα24+ Vβ11+ NKT Cell Numbers Are Decreased in a Wide Variety of Diseases That Are Characterized by Autoreactive Tissue Damage
H. V. Vliet (2001)
10.1084/JEM.194.3.313
Cd1-Restricted Nk T Cells Protect Nonobese Diabetic Mice from Developing Diabetes
B. Wang (2001)
10.4049/jimmunol.166.1.662
Costimulation-Dependent Modulation of Experimental Autoimmune Encephalomyelitis by Ligand Stimulation of Vα14 NK T Cells1
E. Pál (2001)



This paper is referenced by
10.3390/cells10071641
The Role of NKT Cells in Glioblastoma
Emily E. S. Brettschneider (2021)
10.3390/ijms22179520
NKT and NKT-like Cells in Autoimmune Neuroinflammatory Diseases—Multiple Sclerosis, Myasthenia Gravis and Guillain-Barre Syndrome
Michał K Zarobkiewicz (2021)
10.1212/NXI.0000000000001065
Transcriptome and Function of Novel Immunosuppressive Autoreactive Invariant Natural Killer T Cells That Are Absent in Progressive Multiple Sclerosis
Belinda Carrión (2021)
10.3389/fimmu.2021.611795
Immunosuppressive Mechanisms of Regulatory B Cells
D. Catalán (2021)
10.3389/fncel.2021.654284
Connecting Neuroinflammation and Neurodegeneration in Multiple Sclerosis: Are Oligodendrocyte Precursor Cells a Nexus of Disease?
Morgan W. Psenicka (2021)
10.3390/nu13010177
Vitamin D and Immunological Patterns of Allergic Diseases in Children
Agnieszka Lipińska-Opałka (2021)
10.1113/EP087652
The disruption of invariant natural killer T cells exacerbates cardiac hypertrophy and failure caused by pressure overload in mice
Masashige Takahashi (2020)
10.3389/fimmu.2020.00197
The Variable Genomic NK Cell Receptor Locus Is a Key Determinant of CD4+ T Cell Responses During Viral Infection
J. Raynor (2020)
10.1007/978-3-030-54859-9_2
Pathophysiology of Psoriasis/Novel Pathways
J. Hugh (2020)
10.1007/978-3-030-30845-2
Cancer Immunology: A Translational Medicine Context
N. Rezaei (2020)
10.46624/ajptr.2020.v10.i4.024
Clinical Correlation of Taqashshur-E-Jild with Psoriasis: A Literary Approach
S. Sohel (2020)
10.1002/jbm4.10405
Vitamin D and Immune Regulation: Antibacterial, Antiviral, Anti‐Inflammatory
E. Bishop (2020)
Increased TLR 4 Expression Aggravates Sepsis by Promoting IFN-γ Expression in CD 38 − / − Mice
Q. Li (2019)
10.1093/cvr/cvy164
CD1d-dependent natural killer T cells attenuate angiotensin II-induced cardiac remodelling via IL-10 signalling in mice
H. Wang (2019)
10.1038/s41423-019-0221-5
Innate, innate-like and adaptive lymphocytes in the pathogenesis of MS and EAE
L. Van Kaer (2019)
10.1111/bpa.12733
Expression of CD1d by astrocytes corresponds with relative activity in multiple sclerosis lesions
Fraser G W Muir (2019)
10.11648/J.CMR.20190806.12
Natural killer T Cells: A Powerful Via in the Regulation of Non Communicable Chronic Diseases
C. Ramirez-Velazquez (2019)
10.3389/fimmu.2019.00404
Abrogation of Endogenous Glycolipid Antigen Presentation on Myelin-Laden Macrophages by D-Sphingosine Ameliorates the Pathogenesis of Experimental Autoimmune Encephalomyelitis
Yi Ban (2019)
10.3389/fchem.2019.00811
α-Lactosylceramide Protects Against iNKT-Mediated Murine Airway Hyperreactivity and Liver Injury Through Competitive Inhibition of Cd1d Binding
Alan Chuan-Ying Lai (2019)
An investigation into the phenotype, function and immunomodulatory properties of in vitro expanded iNKT cells
Claire Dempsey (2019)
10.1155/2019/3737890
Increased TLR4 Expression Aggravates Sepsis by Promoting IFN-γ Expression in CD38−/− Mice
Q. Li (2019)
10.3389/fncel.2019.00245
NKT Cells in Neurological Diseases
Yu Cui (2019)
10.1007/s11684-018-0622-3
NKT cells in liver diseases
Shasha Zhu (2018)
10.1002/jcp.26250
The role of innate lymphoid cells in health and disease
Hamed Mohammadi (2018)
Update on the pathophysiology of psoriasis.
Jeremy M Hugh (2018)
10.3389/fimmu.2018.00519
Therapeutic Potential of Invariant Natural Killer T Cells in Autoimmunity
L. Van Kaer (2018)
10.1155/2018/8197937
The Role of Invariant NKT in Autoimmune Liver Disease: Can Vitamin D Act as an Immunomodulator?
D. Smyk (2018)
10.1007/s10620-018-5351-6
Evolving Role of Vitamin D in Immune-Mediated Disease and Its Implications in Autoimmune Hepatitis
A. Czaja (2018)
10.12688/f1000research.13794.1
Development of a novel mechanism-based glycolipid adjuvant for vaccination
J. Coelho-dos-Reis (2018)
10.3389/fimmu.2018.01360
Activation and Regulation of B Cell Responses by Invariant Natural Killer T Cells
D. Doherty (2018)
10.1055/s-0037-1602380
Löfgren's Syndrome: Diagnosis, Management, and Disease Pathogenesis.
B. Karakaya (2017)
10.4110/in.2017.17.6.365
Lineage Differentiation Program of Invariant Natural Killer T Cells
D. Kwon (2017)
See more
Semantic Scholar Logo Some data provided by SemanticScholar