Skip to main content

Dendritic cell-expanded, islet-specific CD4+ CD25+ CD62L+ regulatory T cells restore normoglycemia in diabetic NOD mice.

Publication ,  Journal Article
Tarbell, KV; Petit, L; Zuo, X; Toy, P; Luo, X; Mqadmi, A; Yang, H; Suthanthiran, M; Mojsov, S; Steinman, RM
Published in: J Exp Med
January 22, 2007

Most treatments that prevent autoimmune diabetes in nonobese diabetic (NOD) mice require intervention at early pathogenic stages, when insulitis is first developing. We tested whether dendritic cell (DC)-expanded, islet antigen-specific CD4+ CD25+ suppressor T cells could treat diabetes at later stages of disease, when most of the insulin-producing islet beta cells had been destroyed by infiltrating lymphocytes. CD4+ CD25+ CD62L+ regulatory T cells (T reg cells) from BDC2.5 T cell receptor transgenic mice were expanded with antigen-pulsed DCs and IL-2, and were then injected into NOD mice. A single dose of as few as 5x10(4) of these islet-specific T reg cells blocked diabetes development in prediabetic 13-wk-old NOD mice. The T reg cells also induced long-lasting reversal of hyperglycemia in 50% of mice in which overt diabetes had developed. Successfully treated diabetic mice had similar responses to glucose challenge compared with nondiabetic NOD mice. The successfully treated mice retained diabetogenic T cells, but also had substantially increased Foxp3+ cells in draining pancreatic lymph nodes. However, these Foxp3+ cells were derived from the recipient mice and not the injected T reg cells, suggesting a role for endogenous T reg cells in maintaining tolerance after treatment. Therefore, inoculation of DC-expanded, antigen-specific suppressor T cells has considerable efficacy in ameliorating ongoing diabetes in NOD mice.

Duke Scholars

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

January 22, 2007

Volume

204

Issue

1

Start / End Page

191 / 201

Location

United States

Related Subject Headings

  • T-Lymphocytes, Regulatory
  • Prediabetic State
  • Mice, Transgenic
  • Mice, Inbred NOD
  • Mice
  • Male
  • L-Selectin
  • Islets of Langerhans
  • Interleukin-2 Receptor alpha Subunit
  • Insulin
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Tarbell, K. V., Petit, L., Zuo, X., Toy, P., Luo, X., Mqadmi, A., … Steinman, R. M. (2007). Dendritic cell-expanded, islet-specific CD4+ CD25+ CD62L+ regulatory T cells restore normoglycemia in diabetic NOD mice. J Exp Med, 204(1), 191–201. https://doi.org/10.1084/jem.20061631

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

January 22, 2007

Volume

204

Issue

1

Start / End Page

191 / 201

Location

United States

Related Subject Headings

  • T-Lymphocytes, Regulatory
  • Prediabetic State
  • Mice, Transgenic
  • Mice, Inbred NOD
  • Mice
  • Male
  • L-Selectin
  • Islets of Langerhans
  • Interleukin-2 Receptor alpha Subunit
  • Insulin