Natural killer T cells as targets for immunotherapy of autoimmune diseases.

Abstract

CD1d-restricted natural killer T (NKT) cells are innate lymphocytes that play a regulatory role during an immune response. The identification of alpha-galactosylceramide (alpha-GalCer), a marine sponge-derived glycosphingolipid, as a potent stimulator of NKT cells led many laboratories to investigate the effects of NKT cell activation on the regulation of immune responses. These studies revealed that alpha-GalCer induces rapid and robust cytokine production by NKT cells, secondary activation of a variety of innate and adaptive immune cells, and modulation of Th cell responses. Further, alpha-GalCer influences disease progression in a variety of experimental models of autoimmunity and inflammation in mice, including models for type 1 diabetes, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, and atherosclerosis. While these studies have raised significant enthusiasm for manipulation of NKT cells as a means of preventing autoimmunity in the clinical setting, there are significant concerns regarding the safety of repeated alpha-GalCer injections in human subjects.

• Authors: Luc Van Kaer
• Journal: Immunology and cell biology (Immunol Cell Biol) Vol. 82 Issue 3 Pg. 315-22 (Jun 2004) ISSN: 0818-9641 [Print] United States
• PMID: 15186263 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Antigens, CD1
• Antigens, CD1d
• CD1D protein, human
• Cytokines
• Galactosylceramides
• alpha-galactosylceramide

Topics

• Animals
• Antigens, CD1 (immunology)
• Antigens, CD1d
• Autoimmune Diseases (immunology, therapy)
• Cytokines (immunology)
• Galactosylceramides (immunology)
• Humans
• Immunotherapy
• Killer Cells, Natural (immunology, transplantation)
• Lymphocyte Activation (immunology)
• Mice
• T-Lymphocytes (immunology, transplantation)