Dendritic cells with TGF-β1 differentiate naïve CD4 +CD25- T cells into islet-protective Foxp3+ regulatory T cells

Xunrong Luo, Kristin V. Tarbell, Hua Yang, Kathryn Pothoven, Samantha L. Bailey, Ruchuang Ding, Ralph M. Steinman, Manikkam Suthanthiran

Research output: Contribution to journalArticle

185 Citations (Scopus)

Abstract

CD4+CD25+Foxp3+ regulatory T cells (T regs) are important for preventing autoimmune diabetes and are either thymic-derived (natural) or differentiated in the periphery outside the thymus (induced). Here we show that β-cell peptide-pulsed dendritic cells (DCs) from nonobese diabetic (NOD) mice can effectively induce CD4 +CD25+Foxp3+ T cells from naïve islet-specific CD4+CD25- T cells in the presence of TGF-β1. These induced, antigen-specific T regs maintain high levels of clonotype-specific T cell receptor expression and exert islet-specific suppression in vitro. When cotransferred with diabetogenic cells into NOD scid recipients, T regs induced with DCs and TGF-β1 prevent the development of diabetes. Furthermore, in overtly NOD mice, these cells are able to significantly protect syngeneic islet grafts from established destructive autoimmunity. These results indicate a role for DCs in the induction of antigen-specific CD4+CD25+Foxp3+ T cells that can inhibit fully developed autoimmunity in a nonlymphopoenic host, providing an important potential strategy for immunotherapy in patients with autoimmune diabetes.

Original languageEnglish
Pages (from-to)2821-2826
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number8
DOIs
Publication statusPublished - 20 Feb 2007
Externally publishedYes

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Regulatory T-Lymphocytes
Dendritic Cells
Inbred NOD Mouse
Autoimmunity
T-Lymphocytes
Type 1 Diabetes Mellitus
CD4 Antigens
Viral Tumor Antigens
T-Cell Antigen Receptor
Immunotherapy
Thymus Gland
Transplants
Peptides

Keywords

  • Antigen-presenting cells
  • Autoimmunity
  • Nonobese diabetic (NOD) mice
  • Type 1 diabetes

ASJC Scopus subject areas

  • General

Cite this

Dendritic cells with TGF-β1 differentiate naïve CD4 +CD25- T cells into islet-protective Foxp3+ regulatory T cells. / Luo, Xunrong; Tarbell, Kristin V.; Yang, Hua; Pothoven, Kathryn; Bailey, Samantha L.; Ding, Ruchuang; Steinman, Ralph M.; Suthanthiran, Manikkam.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 8, 20.02.2007, p. 2821-2826.

Research output: Contribution to journalArticle

Luo, Xunrong ; Tarbell, Kristin V. ; Yang, Hua ; Pothoven, Kathryn ; Bailey, Samantha L. ; Ding, Ruchuang ; Steinman, Ralph M. ; Suthanthiran, Manikkam. / Dendritic cells with TGF-β1 differentiate naïve CD4 +CD25- T cells into islet-protective Foxp3+ regulatory T cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 8. pp. 2821-2826.
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