title: IDO expressing fibroblasts promote the expansion of antigen specific regulatory T cells.
abstract: 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.
authors.affiliation: BCPFF Burn and Wound Healing Research Group, Department of Surgery, Division of Plastic Surgery, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Terry-Ann
authors.initials: TA
authors.lastname: Curran
authors.forename: Reza Baradar
authors.initials: RB
authors.lastname: Jalili
authors.forename: Ali
authors.initials: A
authors.lastname: Farrokhi
authors.forename: Aziz
authors.initials: A
authors.lastname: Ghahary
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014364:Tryptophan / Q000031:analogs & derivatives / Q000276:immunology / Q000494:pharmacology
chemical_list: D000941:Antigens; D060908:CTLA-4 Antigen; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma; D014364:Tryptophan; C525396:1-methyltryptophan
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