Immature human dendritic cells induce regulatory T cells in vitro

Abstract

Dendritic cells (DCs) are specialized antigen presenting cells that are central players in inititating and directing immune responses. The phenotype and maturation state of DCs are important for their function, and recent studies have highlighted the possibility that distinct DC subsets may differentially regulate immune responses. Now, Jonuleit and colleagues 1xInduction of IL-10-producing, nonproliferating CD4+ T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. Jonuleit, H. et al. J. Exp. Med. 2000; 192: 1213–1222Crossref | PubMed | Scopus (1219)See all References1 have demonstrated that immature and mature DCs induce different types of T cell response, and have reported, for the first time, the induction of human regulatory T cells in vitro.The authors generated immature DCs from human monocytes by culturing them with granulocyte–macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4). These immature DCs (iDCs) were also converted into mature DCs (mDCs) by providing an appropriate maturational stimulus. Repetitive stimulation of CD4+T cells with mDCs resulted in the development of Th1 cells, whereas stimulation with iDCs led to the development of IL-10-producing, non-proliferating T cells. These human T cells resembled murine regulatory T cells and were able to inhibit the antigen-driven proliferation of Th1 cells in a contact- and dose-dependent manner. These results have important implications for DC immunotherapy, as the use of iDCs rather than mDCs might lead to the development of regulatory T cells and tolerance rather than immune stimulation.