The perivascular space as a path of hematopoietic progenitor cells and mature T cells between the blood circulation and the thymic parenchyma

It is known that selected populations of lymphoid cells migrate into and from the adult thymus through blood vessels at the cortico-medullary junction and in the medulla. Here, we show that in the perivascular spaces (PVS) of mice surrounding large blood vessels, CD117-positive hematopoietic progenitor cells, CD4 single-positive (SP) and CD8SP T cells are located. However, developing thymocytes, CD25-positive cells and CD4 and CD8 double-positive cells, are not detectable in the PVS. After intravenous (i.v.) injection of CD117-positive bone marrow (BM) cells from C57BL/6 mice into non-irradiated RAG2 mutant mice Lv., donor-derived cells first preferentially migrate into the PVS within 30 min, and then the number of donor-derived cells in the thymic parenchyma increases. Likewise, newly developed mature T cells in the thymic parenchyma of RAG2 mutant mice transferred with wild-type BM cells migrate to the PVS, before leaving the thymus to the circulation. Accumulation of mature T cells was observed after treatment with sphingosine-1 phosphate receptor agonist FTY720 not only in the medulla but also in the thymic PVS. These results suggest that the PVS is a transit pathway for progenitor cells to immigrate into the thymus and for mature T cells to emigrate from the thymus.