title: The perivascular space as a path of hematopoietic progenitor cells and mature T cells between the blood circulation and the thymic parenchyma.
abstract: 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.
authors.affiliation: Department of Immunology and Microbiology, Meiji University of Oriental Medicine, Hiyoshi-cho, Nantan, Kyoto 629-0392, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Mori
authors.forename: Manami
authors.initials: M
authors.lastname: Itoi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Tsukamoto
authors.forename: Hajime
authors.initials: H
authors.lastname: Kubo
authors.forename: Takashi
authors.initials: T
authors.lastname: Amagai
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000166:cytology*; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000166:cytology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D003094:Collagen / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000737:chemistry / Q000166:cytology; D005353:Fibronectins / Q000032:analysis; D000068876:Fingolimod Hydrochloride; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology* / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D053699:Interleukin-7 Receptor alpha Subunit / Q000032:analysis; D007797:Laminin / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020286:Pericytes / Q000737:chemistry / Q000166:cytology; D011409:Propylene Glycols / Q000494:pharmacology; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D049349:Receptors, Lysosphingolipid / Q000819:agonists / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D013950:Thymus Gland / Q000098:blood supply / Q000166:cytology*
chemical_list: D004268:DNA-Binding Proteins; D005353:Fibronectins; D007166:Immunosuppressive Agents; D053699:Interleukin-7 Receptor alpha Subunit; D007797:Laminin; D011409:Propylene Glycols; C499308:Rag2 protein, mouse; D049349:Receptors, Lysosphingolipid; C102645:laminin alpha 2; D003094:Collagen; D019009:Proto-Oncogene Proteins c-kit; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine