Requirement for extrathymic class I histocompatibility antigens for positive selection of thymus-derived T lymphocytes.

Abstract

We have examined whether the thymus can produce immature T cell precursors for subsequent positive selection in the periphery. Using the intestine as a model system, we demonstrate that extrathymic MHC class I molecules positively select thymus-derived TCR-alpha beta CD8+ intestinal intraepithelial lymphocytes. Grafting of MHC class I+ thymus onto MHC class I- hosts resulted in the generation of donor and host-derived CD4-CD8+ T cells in lymph node, but few TCR-alpha beta CD4-CD8+ intraepithelial lymphocytes. The results indicate that the intestine can act as a site of positive selection for thymus-derived T cells. Bone marrow reconstitution studies demonstrated that non-hematopoietic, radiation-resistant cells, perhaps intestinal epithelial cells, were responsible for extrathymic positive selection of thymus-derived T cells. These findings demonstrate that the thymus can support organ-specific immunity via provision of targeted precursor populations.