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.