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

Abstract

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.