Thymic transplantation across an MHC class I barrier in swine

Thymic tissue transplantation has been performed previously in adult mice t o induce donor-specific tolerance across allogeneic and xenogeneic barriers . We have now attempted to extend this technique to a large animal preclini cal model and describe here our initial studies of allogeneic thymic transp lantation in miniature swine. Two miniature swine were thymectomized before thymic tissue transplantation, and two remained euthymic. Donor thymic tis sue was harvested from SLA class I-mismatched juvenile pigs and placed into recipient sternocephalicus muscle, kidney capsule, and omentum, A 12-day c ourse of cyclosporin A was started on the day of transplantation. Allogenei c thymic engraftment could only be achieved in euthymic and not in thymecto mized miniature swine using this treatment regimen. Both nonthymectomized a nimals showed good graft development, with evidence of thymopoiesis, as ind icated by positive CD1 and host-type SLA class I immunoperoxidase staining of immature graft-infiltrating cells, Both animals also demonstrated donor- specific T cell hyporesponsiveness, as measured by MLR and cell-mediated ly mpholysis. The thymic grafts continued to develop despite the appearance of high levels of anti-donor specific cytotoxic IgG Abs, Thus, thymic tissue transplanted across an SLA class I barrier can engraft and support host thy mopoiesis in euthymic miniature swine. The presence of the host thymus was required for engraftment, These data support the potential of thymic transp lantation as part of a regimen to induce donor-specific tolerance to xenoge neic organ grafts.