Tolerance to liver-specific antigens

Abstract

We have described a TG model for peripheral tolerance of alloreactive CTL. Expression of Q10/L on hepatocytes renders mice functionally tolerant, although in vitro we observe that TG animals have normal numbers of CTL.Pf directed against this antigen. The basis for the tolerance presumably resides in the fact that the TG mice are lacking a subpopulation, either through deletion or anergy, that is responsible for recognition of the antigen on hepatocytes in vivo. The data are consistent with a tolerance model where cells with high affinity receptors are silenced. The presumed low affinity antigen-specific cells remaining in TG mice cannot be primed in vivo when immunized with antigen on spleen cells. Further, these CTL generate poor lytic activity in vitro. This failure to prime TG CTL in vivo could be attributed to primed cells traveling to the liver where they become tolerized when exposed to antigen on hepatocytes. However, we show that TG cells, after transfer to non-TG recipients, cannot be primed in vivo, indicating that the presumed low-affinity cells remaining in TG mice are not readily activable in this milieu. These data also indicate that this tolerance is not readily reversible during a 10- to 17-d time interval.