TOLERANCE AND SUPPRESSION IN A PRIMED IMMUNE-SYSTEM

The induction of tolerance in a primed immune system would be valuable therapeutically, but has been difficult to achieve. Mice primed to mu ltiple minor histoincompatible antigens (miners) are able to rapidly r eject secondary grafts using either their CD4(+) or CD8(+) T-cell subp opulations. Short courses of treatment with nonlytic anti-CD4 and anti -CD8 antibodies targeted at both T-cell subsets can induce long-term p eripheral T-cell tolerance in primed mice. We examine the mechanisms b y which peripheral tolerance is maintained, and show that tolerant mic e harbor CD4(+) T cells capable of specifically suppressing rejection mediated by either subset of primed T cells. Remarkably, elimination o f CD4(+) T cells from tolerant mice resulted in graft rejection, sugge sting that graft-reactive CD8(+) T cells had not been eliminated, but had been under continuous regulation by ''tolerant'' CD4(+) T cells. T his result demonstrates that it may be possible to establish therapeut ic operational tolerance without permanently inactivating all antigen- reactive cells.