Induction of peripheral tolerance among CD8 T cells specific for a self-antigen expressed on pancreatic islet B-cells

Abstract

Transgenic InsHA mice expressing the hemagglutinin (HA) from influenza virus A/PR/8 on pancreatic islet β-cells, demonstrate profound tolerance of the HA and do not develop autoimmunity even if they are immunized with the PR8. Analyses revealed that tolerance was associated with the absence, presumably by deletion, of those CD8+ CTL precursors which demonstrate high avidity for the dominant KdHA epitope. When InsHA mice were mated with the Clone-4 TCR transgenic mouse line which expresses a high affinity KdHA specific TCR the resulting double transgenic neonates developed spontaneous, CD8+ T cell-mediated, autoimmune diabetes and died within 10 days. We suggested that mechanisms of self-tole..