Identification of a novel immunosuppressive dendritic cell population derived from conventional DC (113.5)

Abstract

Abstract Dendritic cells (DC) play a central role in the initiation and regulation of immune responses. Conventional DC (cDC) arise from circulating immediate precursors (pre-cDC) and are currently thought to be terminally differentiated. Here we show, however, that cDC are capable of generating progeny that lost all characteristic features of cDC; and investigate the functional properties of this novel population. Sorted bone marrow pre-cDCs were cultured on a stromal monolayer in the presence/absence of granulocyte-macrophage colony stimulating factor (GM-CSF). On day three, proliferating CD11c+ MHCII+ cDC developed in both cultures. However, in the absence of GM-CSF, these cells gave rise to a homogeneous population of CD11clow MHClow cells (DC-regs) on day 8-10 of culture. In contrast to cDCs, DC-regs failed to up-regulate MHCII and co-stimulatory molecules in response to DC maturation stimuli. DC-regs displayed higher antigen capture capacity but were poor stimulators in T cell proliferation assays. Further, DC-regs not only induced T cell anergy, but also suppressed T cell proliferation in cultures containing immuno-stimulatory DC. Co-transfer of DC-regs with DCs in vivo inhibited T cell proliferation. DC-regs expressed know immunosuppressive molecules such as iNOS, arginase, ICOSL and PD-L1. Our findings challenge the prevalent view that cDC are terminally differentiated, and reveal their potential to generate a regulatory DC population with potent immunosuppressive properties.