Successful Xenogeneic Transplantation in Embryos: Induction of Tolerance by Extrathymic Chick Tissue Grafted into Quail

In previous experiments, we have demonstrated that limb buds engrafted during embryonic life at E4, between MHC-mismatched chick embryos, are not only tolerated after birth, but induce in the recipient a state of split tolerance toward cells expressing the donor MHC haplotype: donor's skin grafts are permanently tolerated while a proliferative response of host's T cells is generated in MLR by donor–type blood cells. If the same experiment is performed, using quail embryo as a donor and chick as a recipient, acute rejection of the quail limb starts during the first two weeks after birth, thus suggesting that the peripheral type of tolerance induced in these experiments can be obtained only in allogeneic but not in xenogeneic combinations. We report here the unexpected result that when a chick limb bud is grafted into a quail at E4, it is tolerated and, like allogeneic grafts in chickens, induces adult skin-graft tolerance without modifying the MLR response. Similar results were obtained with grafts from another closely related species of bird, the guinea fowl from the Phasianidae family. In contrast, xenogeneic combinations involving more distant species (chick and quail as recipients and duck, an Anatidae, as donor) resulted in strong and early rejection from both recipients. As a whole, quails exhibit a greater ability than the chick to become tolerant to antigens presented peripherally from early developmental stages. In adult quails, however, skin grafts performed in either direction (i.e., quail to chick or the reverse) are rejected according to a similar temporal pattern. Moreover, lymphocytes of both species are able to respond equally well to quail or chick IL-2. Several hypotheses are envisaged to account for these observations. It seems likely that this type of tolerance is directly related to antigenic load because the load in chick to quail wing chimeras is larger than that in quail to chick chimeras. This view is supported by the protracted delay in graft rejection observed when two quail wing buds instead of one are grafted into chickens.