Partial tolerance induced by transplantation of spatially separated thymuses: a cue for T cell retolerization in thymus grafts.

Thymus grafts made up of mixed syngeneic and xenogeneic thymus tissues could induce donor-specific tolerance to xenografts with no development of autoimmune syndrome (AIS). But the requirements for the simultaneous presentation of tissue antigens from both species in the process of T cell development in thymus grafts have not hitherto been defined. To do this, we setup a model in which xenothymus grafts from F344 rats were heterotopically implanted into BALB/c nude mice carrying syngeneic thymus grafts, and the grafts were either mixed together or spatially separately; next, we examined the induction of donor-specific tolerance, any pathological changes and the distribution of T lymphocytes. In contrast to the mixed thymus grafts, spatially separated thymus transplants could neither induce a long-term tolerance to skin grafts nor prevent AIS completely. 51Cr-labelled cell-tracing experiments showed that mature peripheral T cells could re-enter into both kinds of thymus grafts, while the T cells isolated from the syngeneic thymus tended to concentrate in the xenothymus grafts. Hence, our data suggest that the immune tolerance induced by mixed thymus transplants could be partially reversed if the thymus tissues from donors and recipients were segregated by spatial telorism. The uneven recirculation of mature T cells might imply that T cells get retolerized within the thymus grafts.