title: Cutting edge: Enhanced IL-2 signaling can convert self-specific T cell response from tolerance to autoimmunity.
abstract: Naive and memory T cells show differences in their response to antigenic stimulation. We examined whether this difference extended to the peripheral deletion of T cells reactive to self-Ag or, alternatively, the induction of autoimmunity. Our results show that although both populations where susceptible to deletion, memory T cells, but not naive T cells, also gave rise to autoimmunity after in vivo presentation of skin-derived self-Ags. The same migratory dendritic cells presented self-Ag to both naive and memory T cell populations, but only the latter had significant levels of the effector molecule granzyme B. Memory T cells also expressed increased levels of the high affinity IL-2 receptor chain after self-Ag recognition. Provision of IL-2 signaling using a stimulatory complex of anti-IL-2 Ab and IL-2 drove the otherwise tolerant naive T cells toward an autoimmune response. Therefore, enhanced IL-2 signaling can act as a major selector between tolerance and autoimmunity.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Waithman
authors.forename: Thomas
authors.initials: T
authors.lastname: Gebhardt
authors.forename: Gayle M
authors.initials: GM
authors.lastname: Davey
authors.forename: William R
authors.initials: WR
authors.lastname: Heath
authors.forename: Francis R
authors.initials: FR
authors.lastname: Carbone
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000502:physiology; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity / Q000502:physiology*; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D053804:Granzymes / Q000276:immunology; D007108:Immune Tolerance / Q000502:physiology*; D007156:Immunologic Memory / Q000502:physiology; D007376:Interleukin-2 / Q000276:immunology*; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000276:immunology; D015398:Signal Transduction; D012867:Skin / Q000166:cytology / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
chemical_list: D001324:Autoantigens; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D053804:Granzymes; C509214:Gzmb protein, mouse