Early appearance of donor-type antigen-presenting cells in the thymuses of 1200 R radiation-induced bone marrow chimeras correlates with self-recognition of donor I region gene products.
The thymus exerts a potent influence on the development of I region self-recognition and antigen recognition by T cells. The mechanism by which the thymus acts on nascent T cells is unknown. It is assumed, however, that a cell interaction between the developing T cell and an la antigen-bearing cell in the thymus is involved. There are several candidates for the critical thymic cell; thymic epithelial, nurse, and antigen-presenting cells (APC) or dendritic cells. Because thymic epithelial cells derive from the third pharyngeal pouch and thymic APC derive from bone marrow, radiation-induced bone marrow chimeras allow the artificial creation of a chimeric thymus gland in which thymic epithelial cells and APC can be genetically different. We made radiation-induced bone marrow chimeras (F1 leads to P) using supralethal radiation doses (1200 R) and found bone marrow donor- (F1) type APC in the thymuses 3 wk after radiation. When such mice fully reconstitute their immune systems, their T cells behave as donor F1 phenotype T cells. Thus, the I region self-restriction and antigen-recognition repertoire of the T cells correlates with the genotype of the bone marrow-derived thymic APC, not the thymic epithelial cell.
D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D004307:Dose-Response Relationship, Radiation; D005802:Genes, MHC Class II / Q000528:radiation effects*; D006801:Humans; D008211:Lymphocyte Cooperation; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D010641:Phenotype; D014176:Protein Biosynthesis / Q000528:radiation effects; D011828:Radiation Chimera; D011946:Receptors, Antigen / Q000235:genetics*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000528:radiation effects; D013997:Time Factors; D014019:Tissue Donors
D011946:Receptors, Antigen