NKT Cells Stimulated by Long Fatty Acyl Chain Sulfatides Significantly Reduces the Incidence of Type 1 Diabetes in Nonobese Diabetic Mice

Sulfatide-reactive type II NKT cells have been shown to regulate autoimmunity and anti-tumor immunity. Although, two major isoforms of sulfatide, C16:0 and C24:0, are enriched in the pancreas, their relative role in autoimmune diabetes is not known. Here, we report that sulfatide/CD1d-tetramer.sup.+...

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Bibliographic Details
Published in:PloS one 2012-05, Vol.7 (5), p.e37771
Main Authors: Subramanian, Lakshmimathy, Blumenfeld, Hartley, Tohn, Robert, Ly, Dalam, Aguilera, Carlos, Maricic, Igor, Mansson, Jan-Eric, Buschard, Karsten, Kumar, Vipin, Delovitch, Terry L
Format: Article
Language:English
Subjects:
Antigens
Autoimmune diseases
Autoimmunity
Biology
Brain research
CD1d antigen
CD4 antigen
Cell activation
Cytokines
Delay
Diabetes
Diabetes mellitus
Drainage
Fatty acids
Immunity
Immunology
Insulin
Interferon
Interleukin 10
Isoforms
Laboratories
Lipids
Lymph nodes
Lymphocytes
Lymphocytes T
Medicine
Mice
Natural killer cells
Pancreas
Rodents
Studies
Sulfatide
T cell receptors
T cells
Type 1 diabetes
Type 2 diabetes
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Summary:Sulfatide-reactive type II NKT cells have been shown to regulate autoimmunity and anti-tumor immunity. Although, two major isoforms of sulfatide, C16:0 and C24:0, are enriched in the pancreas, their relative role in autoimmune diabetes is not known. Here, we report that sulfatide/CD1d-tetramer.sup.+ cells accumulate in the draining pancreatic lymph nodes, and that treatment of NOD mice with sulfatide or C24:0 was more efficient than C16:0 in stimulating the NKT cell-mediated transfer of a delay in onset from T1D into NOD.Scid recipients. Using NOD.CD1d.sup.-/- mice, we show that this delay of T1D is CD1d-dependent. Interestingly, the latter delay or protection from T1D is associated with the enhanced secretion of IL-10 rather than IFN-g by C24:0-treated CD4.sup.+ T cells and the deviation of the islet-reactive diabetogenic T cell response. Both C16:0 and C24:0 sulfatide isoforms are unable to activate and expand type I iNKT cells. Collectively, these data suggest that C24:0 stimulated type II NKT cells may regulate protection from T1D by activating DCs to secrete IL-10 and suppress the activation and expansion of type I iNKT cells and diabetogenic T cells. Our results raise the possibility that C24:0 may be used therapeutically to delay the onset and protect from T1D in humans.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0037771