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.
CITATION STYLE
Illés, Z., Waldner, H., Reddy, J., Bettelli, E., Nicholson, L. B., & Kuchroo, V. K. (2005). T Cell Tolerance Induced by Cross-Reactive TCR Ligands Can Be Broken by Superagonist Resulting in Anti-Inflammatory T Cell Cytokine Production. The Journal of Immunology, 175(3), 1491–1497. https://doi.org/10.4049/jimmunol.175.3.1491
Mendeley helps you to discover research relevant for your work.