A study of peripheral tolerance through embryonic grafts of the bursal epithelial rudiment between MHC-distinct chick embryos.

We report here that different organ grafts are not equally competent to induce tolerance of the host even if they are performed early in development, i.e. before the host's immune system has started to develop. We have grafted the epithelio-mesenchymal rudiment of the bursa of Fabricius between histoincompatible chicken embryos at E5 and found that the transplant is normally colonized by hemopoietic cells from the host and that a normal contingent of B cells is eventually produced. The grafted bursa is tolerated after birth for a few weeks (> or = 4-8) but is in all cases rejected by an immune mechanism which cannot be assimilated to the physiological involution process which occurs at 4-5 months of age. Moreover, even in the first month after birth, when the bursa is still healthy, skin grafts of the same MHC haplotype are promptly rejected. These observations are in contrast with the outcome of allogeneic limb bud grafts which are permanently tolerated after birth although in an unperfect manner. We show in addition that, as was the case in xenogeneic grafts of limb buds and bursas of Fabricius from quail and chick embryos, the allogeneic in situ graft to thymic epithelium of the MHC haplotype of the bursal implant induces tolerance of the bursa. One common point of xenogeneic and allogeneic embryonic grafts of limb bud, bursa and even thymic rudiments is that none of them induced a complete state of tolerance, since proliferation responses were always obtained in vitro in one-way host-donor mixed leucocyte cultures.