CD1-restricted NK T cells protect nonobese diabetic mice from developing diabetes

Citation
B. Wang et al., CD1-restricted NK T cells protect nonobese diabetic mice from developing diabetes, J EXP MED, 194(3), 2001, pp. 313-319
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
JOURNAL OF EXPERIMENTAL MEDICINE
ISSN journal
0022-1007 → ACNP
Volume
194
Issue
3
Year of publication
2001
Pages
313 - 319
Database
ISI
SICI code
0022-1007(20010806)194:3<313:CNTCPN>2.0.ZU;2-S
Abstract
NK T cells are a unique subset of T cells that recognize lipid antigens pre sented by CD Id. After activation, NK T cells promptly produce large amount s of cytokines, which may modulate the upcoming immune responses. Previous studies have documented an association between decreased numbers of NK T ce lls and the progression of some autoimmune diseases, suggesting that NK T c ells may control the development of autoimmune diseases. To investigate the role of NK T cells in autoimmune diabetes, we crossed CD1 knockout (CD1KO) mutation onto the nonobese diabetic (NOD) genetic background. We found tha t male CD1KO NOD mice exhibited significantly higher incidence and earlier onset of diabetes compared with the heterozygous controls. The diabetic fre quencies in female mice showed a similar pattern; however, the differences were less profound between female CD1KO and control mice. Early treatment o f NOD mice with (x-galactosylceramide, a potent NK T cell activator, reduce d the severity of autoimmune diabetes in a CD1-dependent manner. Our result s not only suggest a protective role of CD1-restricted NK T cells in autoim mune diabetes but also reveal a causative link between the deficiency of NK T cells and the induction of insulin-dependent diabetes mellitus.