Cutting edge: Enhanced IL-2 signaling can convert self-specific T cell response from tolerance to autoimmunity.
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.
Waithman
Jason
J
Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Australia.
Gebhardt
Thomas
T
Davey
Gayle M
GM
Heath
William R
WR
Carbone
Francis R
FR
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*
D001324:Autoantigens; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D053804:Granzymes; C509214:Gzmb protein, mouse