IL-12 prevents neonatal induction of transplantation tolerance in mice.
We investigated the effect of IL-12 on the induction of transplantation tolerance by neonatal injection of allogenic cells. We first observed that injection of newborn BALB/c mice with IL-12 and (A/J x BALB/c)F1 spleen cells prevented the Th2 alloimmune response induced by neonatal 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 administration resulted in the emergence of anti-donor cytotoxic T lymphocyte responses although at lower levels than in control uninjected mice. In parallel, we found that mice injected at birth with IL-12 and F1 cells did not develop chimerism and were able to reject a donor-type skin graft 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.
Donckier
V
V
Laboratory of Experimental Immunology, Université Libre des Bruxelles, Brussels, Belgium.
Flamand
V
V
Desalle
F
F
Vanderhaeghen
M L
ML
de Veerman
M
M
Thielemans
K
K
Abramowicz
D
D
Goldman
M
M
D000818:Animals; D000831:Animals, Newborn; D017690:Cell Transplantation; D016207:Cytokines / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D007108:Immune Tolerance; D018664:Interleukin-12 / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018418:Th2 Cells / Q000276:immunology*; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
D016207:Cytokines; D018664:Interleukin-12