Human cord blood stem cell-modulated regulatory T lymphocytes reverse the autoimmune-caused type 1 diabetes in nonobese diabetic (NOD) mice.
BACKGROUND
The deficit of pancreatic islet beta cells caused by autoimmune destruction is a crucial issue in type 1 diabetes (T1D). It is essential to fundamentally control the autoimmunity for treatment of T1D. Regulatory T cells (Tregs) play a pivotal role in maintaining self-tolerance through their inhibitory impact on autoreactive effector T cells. An abnormality of Tregs is associated with initiation of progression of T1D.


RESULTS
Here, we report that treatment of established autoimmune-caused diabetes in NOD mice with purified autologous CD4(+)CD62L(+) Tregs co-cultured with human cord blood stem cells (CB-SC) can eliminate hyperglycemia, promote islet beta-cell regeneration to increase beta-cell mass and insulin production, and reconstitute islet architecture. Correspondingly, treatment with CB-SC-modulated CD4(+)CD62L(+) Tregs (mCD4CD62L Tregs) resulted in a marked reduction of insulitis, restored Th1/Th2 cytokine balance in blood, and induced apoptosis of infiltrated leukocytes in pancreatic islets.


CONCLUSIONS
These data demonstrate that treatment with mCD4CD62L Tregs can reverse overt diabetes, providing a novel strategy for the treatment of type 1 diabetes as well as other autoimmune diseases.
Zhao
Yong
Y
Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America. yongzhao@uic.edu
Lin
Brian
B
Darflinger
Robert
R
Zhang
Yongkang
Y
Holterman
Mark J
MJ
Skidgel
Randal A
RA
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D006943:Hyperglycemia / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology; D019041:L-Selectin / Q000096:biosynthesis; D051379:Mice; D016688:Mice, Inbred NOD; D013234:Stem Cells / Q000166:cytology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
D016207:Cytokines; D019041:L-Selectin