Abstract
Natural killer T (NKT) cells are a subset of lymphocytes that express receptors characteristic of conventional T cells together with receptors typically found on natural killer cells. A key feature of NKT cells is the expression of a semi-invariant T cell receptor that is specific for glycolipid antigens presented by the unusual major histocompatibility complex class I-like molecule CD1d. While their precise immunological functions remain unknown, NKT cells have been implicated in the regulation of adaptive immune responses, including those directed against autoantigens. These findings raise the possibility that specific stimulation of NKT cells may be exploited for therapeutic purposes. A number of laboratories have tested this hypothesis, utilizing the sea sponge-derived agent ?-galactosylceramide (?-GalCer), a specific agonist of NKT cells. Administration of ?-GalCer to mice results in potent activation of NKT cells, rapid and robust cytokine production, and activation of a variety of cells of the innate and adaptive immune systems. Most notably, repeated administration of ?-GalCer to mice favors the generation of conventional T lymphocytes producing T helper (Th) type 2 cytokines such as IL-4 and IL-10. These findings suggest that ?-GalCer can modulate inflammatory conditions that are mediated by pathogenic Th1 cells. Indeed, recent studies have demonstrated that ?-GalCer prevents the development of Type 1 diabetes in non-obese diabetic mice and central nervous system inflammation in mouse models of multiple sclerosis. Collectively, these studies provide a solid foundation for the development of NKT cell ligands as pharmacological agents for treatment of autoimmune diseases.
Keywords: natural killer t cells, cd1d molecules, glycolipids, type 1 diabetes, multiple sclerosis, experimental autoimmune encephalomyelitis, immunomodulation, immunotherapy
Current Pharmaceutical Design
Title: Natural Killer T Cells as Targets for Therapeutic Intervention in Autoimmune Diseases
Volume: 9 Issue: 3
Author(s): M. T. Wilson and L. Van. Kaer
Affiliation:
Keywords: natural killer t cells, cd1d molecules, glycolipids, type 1 diabetes, multiple sclerosis, experimental autoimmune encephalomyelitis, immunomodulation, immunotherapy
Abstract: Natural killer T (NKT) cells are a subset of lymphocytes that express receptors characteristic of conventional T cells together with receptors typically found on natural killer cells. A key feature of NKT cells is the expression of a semi-invariant T cell receptor that is specific for glycolipid antigens presented by the unusual major histocompatibility complex class I-like molecule CD1d. While their precise immunological functions remain unknown, NKT cells have been implicated in the regulation of adaptive immune responses, including those directed against autoantigens. These findings raise the possibility that specific stimulation of NKT cells may be exploited for therapeutic purposes. A number of laboratories have tested this hypothesis, utilizing the sea sponge-derived agent ?-galactosylceramide (?-GalCer), a specific agonist of NKT cells. Administration of ?-GalCer to mice results in potent activation of NKT cells, rapid and robust cytokine production, and activation of a variety of cells of the innate and adaptive immune systems. Most notably, repeated administration of ?-GalCer to mice favors the generation of conventional T lymphocytes producing T helper (Th) type 2 cytokines such as IL-4 and IL-10. These findings suggest that ?-GalCer can modulate inflammatory conditions that are mediated by pathogenic Th1 cells. Indeed, recent studies have demonstrated that ?-GalCer prevents the development of Type 1 diabetes in non-obese diabetic mice and central nervous system inflammation in mouse models of multiple sclerosis. Collectively, these studies provide a solid foundation for the development of NKT cell ligands as pharmacological agents for treatment of autoimmune diseases.
Export Options
About this article
Cite this article as:
Wilson T. M. and Kaer Van. L., Natural Killer T Cells as Targets for Therapeutic Intervention in Autoimmune Diseases, Current Pharmaceutical Design 2003; 9 (3) . https://dx.doi.org/10.2174/1381612033392080
DOI https://dx.doi.org/10.2174/1381612033392080 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Nucleic Acid Enzymes as a Novel Generation of Anti-gene Agents
Current Molecular Medicine Statins Therapy for Connective Tissue Diseases: New Therapeutic Opportunities
Endocrine, Metabolic & Immune Disorders - Drug Targets Biological Therapies of Autoimmune Diseases
Current Drug Targets - Inflammation & Allergy Treatment of Refractory Autoimmune Diseases with Ablative Immunotherapy Using Monoclonal Antibodies and / or High Dose Chemotherapy with Hematopoietic Stem Cell Support
Current Pharmaceutical Design Deciphering the Antibodyome - Peptide Arrays for Serum Antibody Biomarker Diagnostics
Current Proteomics CD26 / Dipeptidyl Peptidase IV: A Regulator of Immune Function and a Potential Molecular Target for Therapy
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Natural and Induced Regulatory T Cells: Targets for Immunotherapy of Autoimmune Disease and Allergy
Inflammation & Allergy - Drug Targets (Discontinued) Immunotherapy-Based Strategies for the Treatment of Autoimmune Diabetes: Searching for the Cure
Current Pharmaceutical Design Toll-Like Receptor Signaling Mechanisms Involved in Dendritic Cell Activation: Potential Therapeutic Control of T Cell Polarization
Current Pharmaceutical Design The Rationale for Comparative Studies of Accelerated Atherosclerosis in Rheumatic Diseases
Current Vascular Pharmacology mTOR Signaling and Metabolic Regulation of T Cells: New Potential Therapeutic Targets in Autoimmune Diseases
Current Pharmaceutical Design Diabetes Mellitus: A Potential Target for Stem Cell Therapy
Current Stem Cell Research & Therapy Clinical Applications and Biosafety of Human Adult Mesenchymal Stem Cells
Current Pharmaceutical Design Clinical Queries Addressed in Patients with Systemic Autoimmune Diseases. Can Cardiovascular Magnetic Resonance Give the Final Solution?
Inflammation & Allergy - Drug Targets (Discontinued) Molecular Characteristics of Autoimmune Pancreatitis
Current Pharmaceutical Design Cot/Tpl-2 Protein Kinase as a Target for the Treatment of Inflammatory Disease
Current Topics in Medicinal Chemistry CD4+CD25+ Regulatory T-Cell Therapy for Allergy, Autoimmune Disease and Transplant Rejection
Inflammation & Allergy - Drug Targets (Discontinued) Autoimmune Diseases in Gastroenterology
Current Pharmaceutical Design Cholecystokinin-8 and Nerve Growth Factor: two Endogenous Molecules Working for the Upkeep and Repair of the Nervous System
Current Drug Targets - CNS & Neurological Disorders Systemic Sclerosis-Related Interstitial Lung Disease
Current Respiratory Medicine Reviews