Double Negative (CD3+4-8-) TCRalphaBeta Splenic Cells from Young NOD Mice Provide Long-Lasting Protection against Type 1 Diabetes
NAVAL MEDICAL RESEARCH CENTER SILVER SPRING MD
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Background Double negative CD34282 TCRab splenic cells DNCD3 can suppress the immune responses to allo and xenografts, infectious agents, tumors, and some autoimmune disorders. However, little is known about their role in autoimmune diabetes, a disease characterized by the reduction of insulin production subsequent to destruction of pancreatic b-cells by a polyclonal population of self-reactive T-cells. Herein, we analyzed the function and phenotype of DNCD3 splenic cells in young NOD mice predisposed to several autoimmune disorders among which, the human-like autoimmune diabetes. MethodologyPrincipal Findings DNCD3 splenic cells from young NOD mice 1 provided long-lasting protection against diabetes transfer in NODScid immunodeficient mice, 2 proliferated and differentiated in the spleen and pancreas of NOD Scid mice and pre-diabetic NOD mice into IL-10-secreting TR-1 like cells in a Th2-like environment, and 3 their antidiabetogenic phenotype is CD3CD42CD82CD28CD69CD25low Foxp32 iCTLA-42TCRab with a predominant Vb13 gene usage. ConclusionsSignificance These findings delineate a new T regulatory component in autoimmune diabetes apart from that of NKT and CD4CD25high Foxp3T-regulatory cells. DNCD3 splenic cells could be potentially manipulated towards the development of autologous cell therapies in autoimmune diabetes.
- Medicine and Medical Research