REQUIREMENT FOR EXTRATHYMIC CLASS-I HISTOCOMPATIBILITY ANTIGENS FOR POSITIVE SELECTION OF THYMUS-DERIVED T-LYMPHOCYTES

We have examined whether the thymus can produce immature T cell precur sors for subsequent positive selection in the periphery, Using the int estine as a model system, we demonstrate that extrathymic MHC class I molecules positively select thymus-derived TCR-alpha beta CD8(+) intes tinal intraepithelial lymphocytes, Grafting of MHC class I+ thymus ont o MHC class I- hosts resulted in the generation of donor and host-deri ved CD4(-)CD8(+) T cells in lymph node, but few TCR-alpha beta CD4(-)C D8(+) intraepithelial lymphocytes, The results indicate that the intes tine can act as a site of positive selection for thymus-derived T cell s. Bone marrow reconstitution studies demonstrated that nonhematopoiet ic, radiation-resistant cells, perhaps intestinal epithelial cells, we re responsible for extrathymic positive selection of thymus-derived T cells, These findings demonstrate that the thymus can support organ-sp ecific immunity via provision of targeted precursor populations.