Human Cord Blood Stem Cell-modulated Regulatory T Lymphocytes Reverse the Autoimmune-caused Type 1 Diabetes in Nonobese Diabetic (NOD) Mice

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2009 Jan 22

PMID 19156219

Citations 34

Authors

Yong Zhao

Brian Lin

Robert Darflinger

Yongkang Zhang

Mark J Holterman

Randal A Skidgel

Affiliations

Soon will be listed here.

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.

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