T cell tolerance induced by cross-reactive TCR ligands can be broken by superagonist resulting in anti-inflammatory T cell cytokine production

Zsolt Illés, Hanspeter Waldner, Jayagopala Reddy, Estelle Bettelli, Lindsay B. Nicholson, Vijay K. Kuchroo

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Cross-reactive activation of potentially autoreactive T cells by high-affinity nonself ligands may be important in breaking self-tolerance in autoimmunity. In a mouse transgenic for a cross-reactive TCR, we have previously shown that a hyperstimulating altered peptide ligand, L144, induced unresponsiveness to the self peptide, proteolipid protein 139-151. In this study, we demonstrate that a superagonist ligand can break T cell tolerance induced by the lower affinity cognate Ag. T cells tolerant to the cognate ligand, Q144, responded to superagonist, L144, by proliferation and the production of mainly IL-4 and IL-10 in vitro. In contrast, T cells that were tolerized to the superagonist were unable to respond to any peptide that cross-reacted with the transgenic TCR. Low-dose immunization with the superagonist L144 was able to break tolerance to the cognate ligand in vivo and resulted in a blunted proliferative response with production of Th2 cytokines.

Original languageEnglish (US)
Pages (from-to)1491-1497
Number of pages7
JournalJournal of Immunology
Volume175
Issue number3
DOIs
StatePublished - Aug 1 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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