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

Overview

MeSH Major

  • Antigens, CD4
  • Cell Differentiation
  • Dendritic Cells
  • Forkhead Transcription Factors
  • Interleukin-2 Receptor alpha Subunit
  • T-Lymphocytes, Regulatory
  • Transforming Growth Factor beta1

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 beta-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-beta1. 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-beta1 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.

publication date

  • February 20, 2007

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1815265

Digital Object Identifier (DOI)

  • 10.1073/pnas.0611646104

PubMed ID

  • 17307871

Additional Document Info

start page

  • 2821

end page

  • 6

volume

  • 104

number

  • 8