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 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.
Fuller
B
B
Division of Rheumatic Diseases, University of Connecticut Health Center, Farmington 06030, USA.
Lefrançois
L
L
D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D016516:CD4-CD8 Ratio; D002454:Cell Differentiation; D006085:Graft Survival / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007422:Intestines / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013934:Thymectomy; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000637:transplantation
D015395:Histocompatibility Antigens Class I; D016693:Receptors, Antigen, T-Cell, alpha-beta