The cellular mechanism of maintenance of neonatally induced tolerance to H-2 class I antigens.

We used limiting dilution analysis protocols to investigate the mechanism by which in vitro cytotoxic T lymphocyte (CTL) hyporeactivity is maintained in adult mice that had been neonatally tolerized to major histocompatibility complex-encoded antigens. Class I molecules, presented on donor cells having an H-2 K or D region haplotype difference from recipients, readily induce tolerogen-specific CTL hyporeactivity. All attempts to identify any in vitro effects of active suppressive cells operative in the maintenance of this hyporeactivity have been unsuccessful. We conclude that this cytotoxic deficiency is the consequence of in vivo mediated clonal inactivation of the precursors of tolerogen-specific CTL. A presentation and evaluation of the assumptions inherent in this conclusion are made. In contrast to class I molecules, class II molecules, presented on donor cells having an H-2 I region haplotype difference from recipients, are unable to induce tolerogen-specific CTL hyporeactivity, even when injected neonatally at high doses. This inability of class II molecules to induce CTL tolerance parallels the considerable difficulty of inducing helper T lymphocyte tolerance to class II molecules.