Helios, and not FoxP3, is the marker of activated Tregs expressing GARP/LAP

摘要: Regulatory T cells (Tregs) are key players of immune regulation/dysregulation both in physiological and pathophysiological settings. Despite significant advances understanding Treg function, there is still a pressing need to define reliable specific markers that can distinguish different subpopulations. Herein we show for the first time activated Tregs [latency associated peptide (LAP) glycoprotein A repetitions predominant (GARP, or LRRC32)] expressed on CD4+FoxP3- expressing Helios (FoxP3-Helios+) steady state. Following TCR activation, GARP/LAP up-regulated CD4+Helios+ regardless FoxP3 expression (FoxP3+/-Helios+). We CD4+GARP+/-LAP+ make IL-10 immunosuppressive cytokine but not IFN-γ effector cytokine. Further characterization FoxP3/Helios subpopulations showed FoxP3+Helios+ proliferate vitro significantly less than FoxP3+Helios- upon stimulation. Unlike Tregs, secrete IL-2, confirming they bona fide with characteristics. Taken together, Helios, FoxP3, marker GARP/LAP, have more suppressive characteristics, compared Tregs. Our work implies therapeutic modalities treating autoimmune inflammatory diseases, allergies graft rejection should be designed induce and/or expand while therapies against cancers infectious diseases avoid such expansion/induction.