IDO expressing fibroblasts promote the expansion of antigen specific regulatory T cells

Immunobiology. 2014 Jan;219(1):17-24. doi: 10.1016/j.imbio.2013.06.008. Epub 2013 Jun 25.


Regulatory CD4(+)CD25(+)Foxp3(+) T cells (Tregs) can be induced and expanded by dendritic cells (DCs) in the presence of the enzyme indoleamine 2,3-dioxygenase (IDO). Here we report that a possible alternative to DCs are IDO expressing dermal fibroblasts (DFs), which are easier to isolate and sustain in culture compared to DCs. When mouse splenocytes were co-cultured with IDO expressing DFs, a significant increase in frequency and the number of Tregs was found compared to those of control group (13.16%±1.8 vs. 5.53%±1.2, p<0.05). Despite observing a higher total number of dead CD4(+) cells in the IDO group, there was a more abundant live CD4(+)CD25(+) subpopulation in this group. Further analysis reveales that these CD4(+) CD25(+) cells have the capacity to expand in the presence of IDO expressing DFs. Greater number of CTLA-4(+) cells and high expression of TGF-β and IL-10 were found in CD4(+) cells of the IDO group compared to those of the controls. This finding confirmed a suppressive functionality of the expanded Tregs. Furthermore, CD4(+) CD25(+) cells isolated from the IDO group showed an alloantigen specific suppressive effect in a mixed lymphocyte reaction assay. These results confirm that IDO expressing dermal fibroblasts can expand a population of suppressive antigen specific Tregs. In conclusion, IDO expressing dermal fibroblasts have the capacity to stimulate the expansion of a subset of Tregs which can be used to generate antigen-specific immune tolerance.

Keywords: Allogeneic immune response; Antigen specific immune tolerance; CD4(+)CD25(+) regulatory T cells; FVB; GCN2; Indolamine 2,3-dioxygenase; Transplantation; Treg; friend leukemia virus B strain; general control non-derepressible 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / immunology
  • Antigens / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CTLA-4 Antigen / immunology
  • CTLA-4 Antigen / metabolism
  • Cell Proliferation*
  • Cells, Cultured
  • Coculture Techniques
  • Fibroblasts / immunology*
  • Fibroblasts / metabolism
  • Flow Cytometry
  • Gene Expression / drug effects
  • Gene Expression / immunology
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / immunology*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Interferon-gamma / immunology
  • Interferon-gamma / pharmacology
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin / cytology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Tryptophan / analogs & derivatives
  • Tryptophan / immunology
  • Tryptophan / pharmacology


  • Antigens
  • CTLA-4 Antigen
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Interleukin-2 Receptor alpha Subunit
  • Transforming Growth Factor beta
  • Interleukin-10
  • Interferon-gamma
  • Tryptophan
  • 1-methyltryptophan