Implantation of cultured thymic fragments in congenitally athymic (nude) rats. Influx of lymphocytes and dendritic cells.

We studied the early events in athymic immunoincompetent rats after implantation with cultured thymic fragments (CTF) under the kidney capsule, with special emphasis on the settlement of lymphocytes and non-lymphoid RT1 class II elements. At 2 weeks after grafting, tissue under the kidney capsule comprises strands of keratin-positive epithelial cells from the graft, without immigrant cells. At 3 weeks, the CTF graft is populated with lymphocytes and with non-lymphoid RT1 class II-positive cells expressing the recipient haplotype (allogeneic combinations). Part of these cells bear determinants recognized by an anti-rat dendritic cell antibody. At 4 weeks the graft exhibits a completely restored thymic architecture. At the periphery, the first indications of T-cell competence generated after CTF implantation are observed 6 weeks after implantation. At 18 weeks, the peripheral thymus-dependent immune system is almost completely developed. This includes in vitro alloreactivity, even to the donor RT1 haplotype of the graft. But skin grafts of the allogeneic CTF donor haplotype are not rejected. Thus, a state of in vivo tolerance is induced under the influence of grafted epithelium, which is not due to a specific deletion of alloreactive cells. We conclude that CTF regain their original thymic architecture between 2 and 4 weeks after implantation in (allogeneic) athymic nude recipients, and that only after this restoration does peripheral thymus-dependent immune competence start to develop.