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Publication : Activation of CD1d-restricted T cells protects NOD mice from developing diabetes by regulating dendritic cell subsets.

First Author  Naumov YN Year  2001
Journal  Proc Natl Acad Sci U S A Volume  98
Issue  24 Pages  13838-43
PubMed ID  11707602 Mgi Jnum  J:72895
Mgi Id  MGI:2153952 Doi  10.1073/pnas.251531798
Citation  Naumov YN, et al. (2001) Activation of CD1d-restricted T cells protects NOD mice from developing diabetes by regulating dendritic cell subsets. Proc Natl Acad Sci U S A 98(24):13838-43
abstractText  CD1d-restricted invariant NKT (iNKT) cells are immunoregulatory cells whose loss exacerbates diabetes in nonobese diabetic (NOD) female mice. Here, we show that the relative numbers of iNKT cells from the pancreatic islets of NOD mice decrease at the time of conversion from peri-insulitis to invasive insulitis and diabetes. Conversely, NOD male mice who have a low incidence of diabetes showed an increased frequency of iNKT cells. Moreover, administration of alpha-galactosylceramide, a potent activating ligand presented by CD1d, ameliorated the development of diabetes in NOD female mice and resulted in the accumulation of iNKT cells and myeloid dendritic cells (DC) in pancreatic lymph nodes (PLN), but not in inguinal lymph nodes. Strikingly, injection of NOD female mice with myeloid DC isolated from the PLN, but not those from the inguinal lymph nodes, completely prevented diabetes. Thus, the immunoregulatory role of iNKT cells is manifested by the recruitment of tolerogenic myeloid DC to the PLN and the inhibition of ongoing autoimmune inflammation.
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