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

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.