Evidence for migration of donor bone marrow stromal cells into recipient thymus after bone marrow transplantation plus bone grafts: A role of stromalcells in positive selection

Objective. Intrathymic T-cell differentiation is characterized by two selec tion events: positive and negative selection. It has been shown that thymic epithelial cells in the cortex are invoiced in the positive selection, whi le macrophages and dendritic cells, derived front hemopoietic stent cells, are involved in the negative selection, Here we investigate whether donor-d erived hone marrow stromal cells can migrate into the thymus and participat e there in positive selection after bone marrow transplantation plus bone g rafts (to recruit bone marrow stromal cells). Methods and Results, Allogeneic bone marrow transplantation with or without bone grafts was carried out in the [C57BL/6-->C3H] combination, Fluorescen ce-activated cell sorter analyses of recipient thymic adherent cells showed that donor-type hone marrow stromal cells exist in the thymus of mice that received bone marrow plus bone grafts but not in the mice that received bo ne marrow cells alone, Histological examination using confocal microscopy a lso confirmed the existence of donor-type stromal cells in the thymus of mi ce that received bone marrow cells plus bones. Both T-cell proliferation an d plaque-forming cell assays indicated that the T cells of such mice show d onor-type major histocompatibility complex-restriction. Conclusion. These findings strongly suggest that stromal cells can migrate from the bone marrow to the thymus, where they participate in the positive selection of thymocytes, (C) 2000 International Society for Experimental He matology, Published by Elsevier Science Inc. Published by Elsevier Science Inc.