Journal
INTERNATIONAL IMMUNOLOGY
Volume 24, Issue 2, Pages 129-136Publisher
OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxr108
Keywords
CD1d; dendritic cell; alpha-GalCer; NKT cell
Categories
Funding
- Ministry of Education, Science, Sports and Culture of Japan [20060013, 20390109]
- Core Research for Evolutional Science and Technology, Japan Science and Technology Agency
- Grants-in-Aid for Scientific Research [20390109, 20060013, 23659203] Funding Source: KAKEN
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Sulfatide-reactive type II NKT cells, the so-called non-invariant NKT (non-iNKT) cells, have been shown to counteract invariant NKT (iNKT) cell activity. However, the effects of sulfatide on activation of iNKT cells by alpha-galactocylceramide (alpha GC) in the context of CD1d have not been studied in detail. Therefore, we studied the blocking effect of sulfatide on alpha GC-induced iNKT cell activation by dendritic cells (DCs). Even in the absence of non-iNKT cells, sulfatide inhibited alpha GC-mediated iNKT cell activation by reducing alpha GC/CD1d complex formations in a dose-dependent manner. This was also confirmed in a cell-free setting using immobilized CD1d-Ig. Moreover, simultaneous injection of alpha GC with sulfatide decreased alpha GC/CD1d complex formations on DCs, accompanied by the reduced CD40L-up-regulation and IFN-gamma production by iNKT cells and IL-12p70 production by DCs. However, sulfatide by itself did not interfere with the presentation of MHC class II-mediated antigen presentation to specific T cells. These results demonstrate that sulfatide competes with alpha GC to be loaded onto CD1d along the endocytic pathway in DCs, thereby inhibiting the iNKT cell response.
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