Double Negative (CD3+4-8-) TCRalphaBeta Splenic Cells from Young NOD Mice Provide Long-Lasting Protection against Type 1 Diabetes
Abstract
Background: Double negative CD3+4282 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. Methodology/Principal Findings: DNCD3 splenic cells from young NOD mice (1) provided long-lasting protection against diabetes transfer in NOD/Scid 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 CD3+(CD42CD82)CD28+CD69+CD25low Foxp32 iCTLA-42TCRab+ with a predominant Vb13 gene usage. Conclusions/Significance: These findings delineate a new T regulatory component in autoimmune diabetes apart from that of NKT and CD4+CD25high Foxp3+T-regulatory cells. DNCD3 splenic cells could be potentially manipulated towards the development of autologous cell therapies in autoimmune diabetes.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 02, 2010
- Accession Number
- ADA551607
Entities
People
- Beverly Duncan
- Constantin Bona
- Cristina Nazarov-stoica
- Jacqueline Surls
- Margaret Kehl
- Sofia Casares
- Teodor Brumeanu
Organizations
- Naval Medical Research Center