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Double negative (CD3+ 4- 8-) TCR alphabeta splenic cells from young NOD mice provide long-lasting protection against type 1 diabetes.


ABSTRACT:

Background

Double negative CD3(+)4(-)8(-) TCR alphabeta 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 beta-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 T(R)-1 like cells in a Th2-like environment, and (3) their anti-diabetogenic phenotype is CD3(+)(CD4(-)CD8(-))CD28(+)CD69(+)CD25(low) Foxp3(-) iCTLA-4(-)TCR alphabeta(+) with a predominant Vbeta13 gene usage.

Conclusions/significance

These findings delineate a new T regulatory component in autoimmune diabetes apart from that of NKT and CD4(+)CD25(high) Foxp3(+)T-regulatory cells. DNCD3 splenic cells could be potentially manipulated towards the development of autologous cell therapies in autoimmune diabetes.

SUBMITTER: Duncan B 

PROVIDER: S-EPMC2896421 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Publications

Double negative (CD3+ 4- 8-) TCR alphabeta splenic cells from young NOD mice provide long-lasting protection against type 1 diabetes.

Duncan Beverly B   Nazarov-Stoica Cristina C   Surls Jacqueline J   Kehl Margaret M   Bona Constantin C   Casares Sofia S   Brumeanu Teodor-D TD  

PloS one 20100702 7


<h4>Background</h4>Double negative CD3(+)4(-)8(-) TCR alphabeta 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 beta-cells by a polyclonal population of self-reactive T-cells. Herein, we analyzed the function and phenotype of DNCD3 splenic c  ...[more]

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