Cutting edge: Enhanced IL-2 signaling can convert self-specific T cell response from tolerance to autoimmunity

The Journal of Immunology : Official Journal of the American Association of Immunologists
Jason WaithmanFrancis R Carbone

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.

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Citations

Apr 4, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laura S BurschKristin A Hogquist
Feb 15, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kevin S GoudyRoland Tisch
Apr 26, 2016·The Journal of Clinical Investigation·Andreas KupzStefan H E Kaufmann
Nov 13, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Salvatore FiorenzaIan H Frazer
Sep 10, 2008·Journal of Clinical Immunology·Calliope A Dendrou, Linda S Wicker
May 11, 2011·Immunotherapy·Courtney Nicholas, Gregory B Lesinski
Oct 29, 2013·Nature Immunology·Laura K MackayThomas Gebhardt
Oct 19, 2016·Immunology and Cell Biology·Mayura V Wagle, Ian A Parish
Oct 20, 2020·Frontiers in Immunology·Simone NüssingIan A Parish
Nov 3, 2016·Cancer Immunology Research·Lauryn E KlevornRyan M Teague
May 1, 2021·ELife·Emily N TruckenbrodStephen C Jameson

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