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

• Published in: International immunology Vol. 19; no. 6; pp. 745 - 753
• Main Authors: Mori, Kazuya, Itoi, Manami, Tsukamoto, Noriyuki, Kubo, Hajime, Amagai, Takashi
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.06.2007; Oxford Publishing Limited (England)
• Subjects: Animals; Basement Membrane - cytology; CD4-Positive T-Lymphocytes - chemistry; CD4-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - chemistry; CD8-Positive T-Lymphocytes - cytology; Cell Movement - drug effects; Cell Movement - immunology; cell trafficking; Collagen - analysis; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Endothelial Cells - chemistry; Endothelial Cells - cytology; Fibronectins - analysis; Fingolimod Hydrochloride; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells - chemistry; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - immunology; Immunosuppressive Agents - pharmacology; Interleukin-7 Receptor alpha Subunit - analysis; Laminin - analysis; mature T cells; Mice; Mice, Inbred C57BL; Mice, Knockout; mouse; Organization; Pericytes - chemistry; Pericytes - cytology; Propylene Glycols - pharmacology; Proto-Oncogene Proteins c-kit - analysis; Receptors, Lysosphingolipid - agonists; Receptors, Lysosphingolipid - metabolism; Sphingosine - analogs & derivatives; Sphingosine - pharmacology; T progenitor; T-Lymphocytes - chemistry; T-Lymphocytes - cytology; T-Lymphocytes - metabolism; thymus; Thymus Gland - blood supply; Thymus Gland - cytology; mouse; cell trafficking; thymus; Organization; T progenitor; mature T cells
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxm041

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 i.v., 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.