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

AUTOR(ES)

Naumov, Yuri N.

FONTE

The National Academy of Sciences

RESUMO

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 α-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.

Documentos Relacionados

• CD1d-restricted T cell activation by nonlipidic small molecules
• Role of CD1d-Restricted NKT Cells in Microbial Immunity
• CD1d-restricted T cells regulate dendritic cell function and antitumor immunity in a granulocyte–macrophage colony-stimulating factor-dependent fashion
• Mycobacterial phosphatidylinositol mannoside is a natural antigen for CD1d-restricted T cells
• Critical Proinflammatory and Anti-Inflammatory Functions of Different Subsets of CD1d-Restricted Natural Killer T Cells during Trypanosoma cruzi Infection