TOLERANCE INDUCTION AS A MULTISTEP PROCESS

Tolerant T cells are characterized by their partial or full resistance to activation by antigen. We investigated whether tolerant T cells we re still receptive to further tolerogenic signals. T cells expressing a transgenic T cell receptor (TCR) specific for the major histocompati bility complex (MHC) class I molecule Kb were deleted in mice carrying Kb but not ill mice expressing the mutant Kb-molecule K-bm1 [TCR (H-2 (bm1xk)) mice]. These T cells were tolerant in vivo but could be activ ated in vitro by the Kb antigen. This in vitro reactivity was abolishe d after the tolerant T cells encountered Kb-positive cells that had be en intravenously injected. Furthermore, in TCR (H-2(bm1xk)) mice expre ssing Kb only on hepatocytes, no T lymphocytes bearing the transgenic TCR could be found in the periphery, indicating that the additional co ntact with Kb on hepatocytes led to deletion of the tolerant T cells. These findings demonstrate that tolerance induction can be a multi-ste p process.