Single cell suppression profiling of human regulatory T cells 2892

Abstract Description Regulatory T cells (Tregs) play an important role in regulating immune homeostasis in health and disease. Traditionally their suppressive function has been assayed by mixing purified cell populations, which does not provide an accurate picture of a physiologically relevant response. To overcome this limitation, we here develop ‘single cell suppression profiling of human Tregs’ (scSPOT). scSPOT uses a 52-marker CyTOF panel, a cell division detection algorithm, and a whole PBMC system to assess the effect of Tregs on all other cell types simultaneously. In this head-to-head comparison, we find Tregs having the clearest suppressive effects on CD8-EM through partial division arrest, cell cycle inhibition, and effector molecule downregulation. Additionally, scSPOT identifies a Treg phenotypic split previously observed in viral infection, and propose modes of action by the FDA-approved drugs Ipilimumab and Tazemetostat. scSPOT is thus scalable, robust, widely applicable, and may be used to better understand Treg immunobiology and screen for therapeutic compounds. Funding Sources This work was supported by the Japan Society for the Promotion of Science 23K11304, Nippon Foundation (JBW), Takeda Foundation (JBW), Japan Society for the Promotion of Science 16H06295 (SS), Japan Agency for Medical Research and Development JP19gm0010005 (SS), and Leading Advanced Projects for Medical Innovation (SS) Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)