LEVELS OF PERIPHERAL T-CELL TOLERANCE INDUCED BY DIFFERENT DOSES OF TOLEROGEN

Antigen-specific immunosuppression requires an understanding of the pa rameters that control peripheral T cell tolerance. A liver-specific in ducible promoter was used to drive the expression of the major histoco mpatibility complex antigen K(b) in transgenic mice. Minute amounts of K(b), expressed exclusively on hepatocytes, induced tolerance by part ial down-regulation of the T cell receptor (TCR) on the self-reactive CD8+ cells. Contact of these tolerant T cells with high concentrations of K(b) after induction led to complete down-regulation of TCR. Thus, tolerant T cells are susceptible to further tolerogenic signals and r each different levels of tolerance depending on antigen dose.