Induction of FoxP3+CD4+CD25+ regulatory T cells by a bone marrow population distinct from plasmacytoid-DC

Abstract

Facilitating cells (FC) are bone marrow-derived cells that facilitate allogeneic hematopoietic stem cell (SC) engraftment and induce transplantation tolerance without causing graft vs. host disease. Although there is evidence for FC directing the development of FoxP3+CD4+CD25+ regulatory T cells, the specific FC subsets that control regulatory T cell development have not been defined. The current study investigates the role of FC-CD3epsilon+ and FC-CD3epsilon- subpopulations in the development of FoxP3+CD4+CD25+ regulatory T cells. Here, we demonstrate that the induction of FoxP3+CD4+CD25+ regulatory T cells in coculture is mediated by not only the FC-CD3epsilon- subset but also the FC-CD3epsilon+ subset, which is distinct from plasmacytoid precursor dendritic cells (p-preDC). The identification of cell populations distinct from p-preDC that efficiently induce the generation of FoxP3+CD4+CD25+ regulatory T cells may prove useful for future therapeutic applications for the induction of tolerance following allogeneic SC transplantation.