title: Expression of CCR9 in HTLV-1+ T cells and ATL cells expressing Tax.
abstract: Adult T-cell leukemia (ATL) is a highly aggressive mature CD4+ T-cell malignancy that is etiologically associated with human T-lymphotropic virus Type 1 (HTLV-1). ATL is characterized by frequent infiltration of lymph nodes, spleen, liver, skin and gut. Previously, we and others have shown that the majority of ATL cases are strongly positive for CCR4, which may explain the frequent skin invasion of ATL. Here, we examined whether ATL cells express CCR9, which is involved in T-cell homing to the gastrointestinal tract. Human T cell lines carrying HTLV-1 consistently expressed CCR9 together with the HTLV-1-encoded transcriptional activator Tax. Although ATL cells freshly isolated from peripheral blood hardly expressed CCR9, ATL cells cultured for 1 day consistently expressed CCR9 in parallel with the upregulation of Tax. Induction of Tax by Cd2+ in JPX-9, a subline of Jurkat human T cell line carrying Tax under the control of metallothionein promoter, led to upregulation of CCR9. A luciferase reporter gene under the control of the CCR9 promoter was expressed by cotransfection of an expression vector for Tax or in Cd2+-treated JPX-9 cells. Furthermore, immunohistochemical staining demonstrated that ATL cells infiltrating gastrointestinal tract were frequently positive for CCR9. Collectively, CCR9 is inducible in ATL cells expressing Tax and may play a role in the gastrointestinal involvement of ATL.
authors.affiliation: Department of Microbiology and SORST, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nagakubo
authors.forename: Zhe
authors.initials: Z
authors.lastname: Jin
authors.forename: Kunio
authors.initials: K
authors.lastname: Hieshima
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakayama
authors.forename: Aiko-Konno
authors.initials: AK
authors.lastname: Shirakawa
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Tomayoshi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Tsukasaki
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Yamada
authors.forename: Osamu
authors.initials: O
authors.lastname: Yoshie
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002461:Cell Line, Transformed / Q000378:metabolism / Q000473:pathology / Q000821:virology; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000378:metabolism* / Q000473:pathology; D008156:Luciferases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D054388:Receptors, CCR; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology / Q000821:virology
chemical_list: C119309:CC chemokine receptor 9; C515354:CCR4 protein, human; D016356:Gene Products, tax; D054388:Receptors, CCR; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D008156:Luciferases