Levels of Peripheral T Cell Tolerance Induced by Different Doses of Tolerogen

Antigen-specific immunosuppression requires an understanding of the parameters that control peripheral T cell tolerance. A liver-specific inducible promoter was used to drive the expression of the major histocompatibility complex antigen K$^b$ in transgenic mice. Minute amounts of K$^b$, expressed exclusively on hepatocytes, induced tolerance by partial 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 reach different levels of tolerance depending on antigen dose.