IL-12 PREVENTS NEONATAL INDUCTION OF TRANSPLANTATION TOLERANCE IN MICE

We investigated the effect of IL-12 on the induction of transplantatio n tolerance by neonatal injection of allogenic cells. We first observe d that injection of newborn BALB/c mice with IL-12 and (A/J x BALB/c)F 1 spleen cells prevented the Th2 alloimmune response induced by neonat al inoculation of F1 cells alone and allowed the differentiation of T cells secreting high amounts of IL-2 and IFN-gamma in mixed lymphocyte cultures with donor-type stimulators. Furthermore, IL-12 administrati on resulted in the emergence of anti-donor cytotoxic T lymphocyte resp onses although at lower levels than in central uninjected mice. In par allel, we found that mice injected at birth with IL-12 and F1 cells di d not develop chimerism and were able to reject a donor-type skin graf t as efficiently as control mice. We conclude that IL-12 inhibits the Th2 polarization of the newborn response to alloantigens and prevents thereby the establishment of transplantation tolerance.