title: IL-2 coordinates IL-2-producing and regulatory T cell interplay.
abstract: Many species of bacteria use quorum sensing to sense the amount of secreted metabolites and to 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 (IL-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 (T reg) cells, 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 T reg 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 T reg 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 T reg cells as CD4(+) T cells restrain their growth by monitoring IL-2 levels, thereby preventing uncontrolled responses and autoimmunity.
authors.affiliation: Unité de Biologie des Populations Lymphocytaires, Department of Immunology, Institut Pasteur, Paris, France.
authors.forename: Inês F
authors.initials: IF
authors.lastname: Amado
authors.forename: Julien
authors.initials: J
authors.lastname: Berges
authors.forename: Rita J
authors.initials: RJ
authors.lastname: Luther
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Mailhé
authors.forename: Sylvie
authors.initials: S
authors.lastname: Garcia
authors.forename: Antonio
authors.initials: A
authors.lastname: Bandeira
authors.forename: Casey
authors.initials: C
authors.lastname: Weaver
authors.forename: Adrian
authors.initials: A
authors.lastname: Liston
authors.forename: Antonio A
authors.initials: AA
authors.lastname: Freitas
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology / Q000378:metabolism; D025461:Feedback, Physiological; D005260:Female; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017634:Self Tolerance; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000276:immunology* / Q000378:metabolism
chemical_list: D007376:Interleukin-2; D049452:Green Fluorescent Proteins