Quorum sensing in CD4+ T cells homeostasis : IL-2 coordinates the interplay between IL-2p and regulatory T cells.. Mus musculus

Many species of bacteria use quorum sensing to sense the amounts of secreted metabolites and adapt their growth according to their population density. We asked whether similar mechanisms would operate in lymphocyte homeostasis. We investigated the regulation of the size of Interleukin-2-producing CD4+ T-cell (IL-2p) pool using different IL-2-reporter mice. We found that in the absence of either IL-2 or regulatory CD4+ T-cells (Treg) the number of IL-2p-cells increases. Administration of IL-2 decreases the number of cells of the IL-2p-cell subset and pertinently, abrogates their ability to produce IL-2 upon in vivo cognate stimulation, while increasing Treg-cell numbers. We propose that control of the IL-2p-cell numbers occurs via a quorum-sensing-like feedback loop where the produced IL-2 is sensed by both the activated CD4+ T-cell pool and by Treg-cells, which reciprocally regulate cells of the IL-2p-cell subset. In conclusion, IL-2 acts as a self-regulatory circuit integrating the homeostasis of activated and regulatory T cells as CD4+ T-cells restrain their growth by monitoring IL-2 levels thereby preventing uncontrolled responses and autoimmunity. Overall design: 2 populations of conventional CD4+ T cell are analysed. 5 replicates for each. GFP- is the control one.