Evidence for peripheral mechanisms inducing tissue tolerance during ontogeny.

Tissue grafts from a histoincompatible donor of the same developmental stage were introduced into an early chick embryo host in order to probe the immune response to the graft after birth, when the host has reached immune maturity. Limb buds from B4 or B12 chicken strains were grafted in situ on (B15 x B21)F1 recipients that were allowed to hatch. The grafted wing grew normally and was tolerated in a nearly perfect way during the host's lifetime, although reversible rejection crises severely affected the fundamentally healthy state of the grafted tissues. Skin grafts of the same major histocompatibility complex haplotype as the wing were performed on the adult wing-chimera and were permanently tolerated. In contrast, host peripheral blood lymphocytes maintained their capacity to proliferate against donor cells in the mixed lymphocyte reaction. These results, while showing that in vitro and in vivo tolerance are separable phenomena, suggest the existence of a peripheral mechanism inducing tolerance to self that complements the elimination of self-reactive clones by the thymus.