title: Engraftment and dissemination of T lymphocytes from primary haemophagocytic lymphohistiocytosis in scid mice.
abstract: Although primary haemophagocytic lymphohistiocytosis (HLH) is a genetic disorder of T lymphocytes, it remains unclear why T lymphocytes of primary HLH patients preferentially infiltrate the central nervous system and peripheral blood, in addition to the reticuloendothelial systems. We engrafted Herpesvirus saimiri (HVS)-immortalized T-lymphocyte lines established from primary HLH patients into severe combined immunodeficient (scid) mice and examined their capacity to infiltrate mouse organs. A diffuse infiltration of human T lymphocytes was detected in each organ of scid mice treated with 1 x 10(6) T lymphocytes from all four primary HLH patients assessed, whereas no infiltration of T lymphocytes from healthy individuals was observed in any organ. The infiltration of T lymphocytes was mainly observed in the lung, brain and peripheral blood, in association with haemophagocytosis. These cells were positive for HLA-DR, CD3 and either CD8 or CD4, but negative for CD68. Certain markers of proliferation and apoptotic activities were highly positive in these cells. There was no difference between the infiltration pattern of T lymphocytes of primary HLH patients with a perforin deficiency and those without. By Southern blot analysis, T lymphocytes infiltrating mouse organs were observed to be polyclonal. These findings suggest that our murine model implementing HVS-immortalized human T lymphocytes is suitable to clarify the pathogenesis of primary HLH.
authors.affiliation: Department of Paediatrics, Saga Medical School, Saga, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yoshida
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishii
authors.forename: Koichi
authors.initials: K
authors.lastname: Oshima
authors.forename: Fumio
authors.initials: F
authors.lastname: Yanai
authors.forename: Atushi
authors.initials: A
authors.lastname: Ogawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kataoka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sako
authors.forename: Yong Dong
authors.initials: YD
authors.lastname: Park
authors.forename: Kayoko
authors.initials: K
authors.lastname: Koide
authors.forename: Miyoko
authors.initials: M
authors.lastname: Imayoshi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Zaitsu
authors.forename: Kenji
authors.initials: K
authors.lastname: Muraoka
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Hamasaki
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Imashuku
authors.forename: Masaki
authors.initials: M
authors.lastname: Yasukawa
mesh_terms: D000818:Animals; D015139:Blotting, Southern; D001921:Brain / Q000276:immunology; D016022:Case-Control Studies; D002461:Cell Line, Transformed; D002465:Cell Movement; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D005434:Flow Cytometry; D015616:Histiocytosis, Non-Langerhans-Cell / Q000276:immunology*; D006801:Humans; D007223:Infant; D008168:Lung / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D023421:Models, Animal; D013601:T-Lymphocytes / Q000502:physiology* / Q000637:transplantation