Natural killer T cells as targets for immunotherapy of autoimmune diseases

L Van Kaer - Immunology and cell biology, 2004 - Wiley Online Library
Immunology and cell biology, 2004Wiley Online Library
CD1d‐restricted natural killer T (NKT) cells are innate lymphocytes that play a regulatory
role during an immune response. The identification of α‐galactosylceramide (α‐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 α‐GalCer induces rapid and robust cytokine
production by NKT cells, secondary activation of a variety of innate and adaptive immune …
CD1d‐restricted natural killer T (NKT) cells are innate lymphocytes that play a regulatory role during an immune response. The identification of α‐galactosylceramide (α‐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 α‐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, α‐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 α‐GalCer injections in human subjects.
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