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


RESULTS
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
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.
Duncan
Beverly
B
National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
Nazarov-Stoica
Cristina
C
Surls
Jacqueline
J
Kehl
Margaret
M
Bona
Constantin
C
Casares
Sofia
S
Brumeanu
Teodor-D
TD
D000818:Animals; D017252:CD3 Complex / Q000378:metabolism*; D015704:CD4 Antigens / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta