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PLoS One. 2009;4(1):e4226. doi: 10.1371/journal.pone.0004226. Epub 2009 Jan 19.

Human cord blood stem cell-modulated regulatory T lymphocytes reverse the autoimmune-caused type 1 diabetes in nonobese diabetic (NOD) mice.

Author information

1
Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America. yongzhao@uic.edu

Abstract

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.

METHODOLOGY/PRINCIPAL FINDINGS:

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/SIGNIFICANCE:

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.

PMID:
19156219
PMCID:
PMC2627485
DOI:
10.1371/journal.pone.0004226
[Indexed for MEDLINE]
Free PMC Article

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