Characterization of thymus-seeding precursor cells from mouse bone marrow

The nature of the cells that seed the thymus of an irradiated recipient aft er intravenous (IV) transfer of bone marrow (BM) cells was investigated usi ng 2 approaches. First, direct entry of a small number of donor BM cells in to the thymus was tracked using a Ly-5 marker. Second, secondary IV transfe r of the seeded thymus cells into a secondary recipient was used as an assa y for precursor activity. A range of cell types was found to enter the reci pient thymus initially, including B-lineage cells and myeloid cells, but T precursors were undetectable by flow cytometry over the first few days. Alt hough all cells initially entering the thymus proliferated, no sustained th ymus reconstitution was seen until day 4, when recognizable T-lineage precu rsors began to appear. The secondary transfer assays revealed the presence of lymphoid precursors in the recipient thymus, including T, NKT, NK, and B precursor activity, with a notable early burst of B-lineage generative cap acity. There was no evidence of sustained myeloid precursor or multipotent stem cell activity, even though these were seen if BM cells were injected d irectly into the recipient thymus rather than introduced into the bloodstre am. It is concluded that even though many cell types may initially enter an irradiated thymus, the thymus acts as a sieve, allowing lymphoid precursor s, but not multipotent stem cells, to seed the environmental niches that pe rmit selected precursor cell development and thymus reconstitution. (C) 200 1 by The American Society of Hematology.