Differential Kinetics of Various Subsets of Thymic Bone Marrow-Derived Stromal Cells in Rat Chimeras

Identification of those cells within the thymic stroma which are responsible for tolerance induction remains controversial. Evidence derived from studies of bone marrow chimeras or thymus transplants attributed this function to cells of haematopoietic origin, usually class II positive medullary dendritic cells (DC). Recent data suggest, however, that a stromal element located in the thymus cortex might be involved in negative selection. To further explore this issue we used immunohistology and immunocytology with a combination of allotype and cell type specific monoclonal antibodies (MoAb) to study the turnover of thymic stromal cells of haematopoietic origin in different rat models of allogeneic and congenic bone marrow (BM) radiation chimeras. Use of CFU-GM cultured BM inoculum for congenic recipients allowed us to distinguish between direct homing of donor myeloid cells and the delayed migration of the donor stem cell progeny after the post-irradiation recovery of the recipient. Our data indicate a heterogeneity in the turnover rate of thymic mobile stromal cells. While DC and a subset of macrophages located in the cortex as well as in the medulla (ED1+), within 4 weeks were virtually all of donor type, cortical macrophages detected by ED2 MoAbs were still incompletely replaced after a period as long as 20 weeks. Slow turnover, location and variable class II expression may imply a role for thymic cortical macrophages in (self-) tolerance induction.