Development of stem cell-derived antigen-specific regulatory T cells against autoimmunity

Mohammad Haque, Kristin Fino, Praneet Sandhu, Jianxun Song

Research output: Contribution to journalArticle

Abstract

Autoimmune diseases arise due to the loss of immunological self-tolerance. Regulatory T cells (Tregs) are important mediators of immunologic self-tolerance. Tregs represent about 5 - 10% of the mature CD4+ T cell subpopulation in mice and humans, with about 1 - 2% of those Tregs circulating in the peripheral blood. Induced pluripotent stem cells (iPSCs) can be differentiated into functional Tregs, which have a potential to be used for cell-based therapies of autoimmune diseases. Here, we present a method to develop antigen (Ag)-specific Tregs from iPSCs (i.e., iPSC-Tregs). The method is based on incorporating the transcription factor FoxP3 and an Ag-specific T cell receptor (TCR) into iPSCs and then differentiating on OP9 stromal cells expressing Notch ligands delta-like (DL) 1 and DL4. Following in vitro differentiation, the iPSC-Tregs express CD4, CD8, CD3, CD25, FoxP3, and Ag-specific TCR and are able to respond to Ag stimulation. This method has been successfully applied to cell-based therapy of autoimmune arthritis in a murine model. Adoptive transfer of these Ag-specific iPSC-Tregs into Ag-induced arthritis (AIA)-bearing mice has the ability to reduce joint inflammation and swelling and to prevent bone loss.

Original languageEnglish (US)
Article numbere54720
JournalJournal of Visualized Experiments
Volume2016
Issue number117
DOIs
StatePublished - Nov 8 2016

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Induced Pluripotent Stem Cells
T-cells
Regulatory T-Lymphocytes
Antigens
Stem cells
Autoimmunity
Stem Cells
Self Tolerance
Cell- and Tissue-Based Therapy
T-Cell Antigen Receptor
Autoimmune Diseases
Arthritis
Bearings (structural)
Interleukin-2 Receptor alpha Subunit
Transcription factors
Adoptive Transfer
Stromal Cells
Swelling
Bone
Blood

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Chemical Engineering(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Haque, Mohammad ; Fino, Kristin ; Sandhu, Praneet ; Song, Jianxun. / Development of stem cell-derived antigen-specific regulatory T cells against autoimmunity. In: Journal of Visualized Experiments. 2016 ; Vol. 2016, No. 117.
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Development of stem cell-derived antigen-specific regulatory T cells against autoimmunity. / Haque, Mohammad; Fino, Kristin; Sandhu, Praneet; Song, Jianxun.

In: Journal of Visualized Experiments, Vol. 2016, No. 117, e54720, 08.11.2016.

Research output: Contribution to journalArticle

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