Transplantation tolerance induced in foetal mouse thymus in vitro

Abstract

BURNET'S suggestion that self tolerance was gained during foetal life by elimination of self reactive clones of lymphocytes¹ has gained support from studies with lymphoid chimaeras prepared by injection of either foetal or neonatal animals with histoincompatible spleen cells²; by injection of irradiated adult F₁ hybrid mice with parental-type bone marrow cells³, or by fusion of eight-cell-stage embryos⁴. However, in some situations active suppression by blocking factors⁵ or by suppressor T cells⁶ may account for the lack of reactivity in apparently tolerant animals, although it is likely that these mechanisms operate only when tolerance is incompletely induced⁷. We describe here an in vitro model for the study of transplantation tolerance and offer evidence that active suppression by regulatory T cells is not involved. Unresponsiveness to mixed lymphocyte culture (MLC)-stimulating determinants on histoincompatible cells was induced in foetal murine thymocytes in organ culture by incubation of foetal thymus, of 14-d gestation, in contact with mitomycin-treated fragments of adult allogeneic spleen (Fig. 1).