title: Cutting edge: IL-2 signals determine the degree of TCR signaling necessary to support regulatory T cell proliferation in vivo.
abstract: To ensure immune tolerance, regulatory T cell (Treg) numbers must be maintained by cell division. This process has been thought to be strictly dependent on the Treg TCR interacting with MHC class II. In this study, we report that Treg division does not absolutely require cell-autonomous TCR signaling in vivo, depending on the degree of IL-2-mediated stimulation provided. At steady state IL-2 levels, Tregs require cell-autonomous TCR signaling to divide. However, when given exogenous IL-2 or when STAT5 is selectively activated in Tregs, Treg division can occur independently of MHC class II and TCR signaling. Thus, depending on the amount of IL-2R stimulation, a wide range of TCR signals supports Treg division, which may contribute to preservation of a diverse repertoire of Treg TCR specificities. These findings also have therapeutic implications, as TCR signaling by Tregs may not be required when using IL-2 to increase Treg numbers for treatment of inflammatory disorders.
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Zou
authors.forename: Atsushi
authors.initials: A
authors.lastname: Satake
authors.forename: Evann
authors.initials: E
authors.lastname: Corbo-Rodgers
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Schmidt
authors.forename: Michael A
authors.initials: MA
authors.lastname: Farrar
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Maltzman
authors.forename: Taku
authors.initials: T
authors.lastname: Kambayashi
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
chemical_list: D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2