title: Decreased CXCR3 expression in CD4+ T cells exposed to asbestos or derived from asbestos-exposed patients.
abstract: Asbestos causes malignant tumors such as lung cancer and malignant mesothelioma (MM). To determine whether asbestos exposure causes reduction of antitumor immunity, we established an in vitro T-cell line model of low-dose and continuous exposure to asbestos using an human adult T-cell leukemia virus-1 immortalized human polyclonal T-cell line, MT-2, and revealed that MT-2 cells exposed continuously to asbestos showed resistance to asbestos-induced apoptosis. In addition, the cells presented reduction of surface CXCR3 chemokine receptor expression and IFN-γ production. In this study, to confirm that these findings are suitable for clinical translation, surface CXCR3 and IFN-γ expression were analyzed using freshly isolated human CD4(+) T cells derived from healthy donors and patients with pleural plaque (PP) or MM. The results revealed that CXCR3 and IFN-γ expression in the ex vivo model were reduced in some cases. Additionally, CXCR3 expression in CD4(+) T cells from PPs and MMs was significantly reduced compared with that from healthy donors, and CD4(+) T cells from patients with MMs exhibited a marked reduction in IFN-γ mRNA levels after stimulation in vitro. Moreover, CD4(+)CXCR3(+) T cells in lymphocytes from MMs showed a tendency for an inverse correlation with its ligand CXCL10/IP10 in plasma. These findings show reduction of antitumor immune function in asbestos-exposed patients and indicate that CXCR3, IFN-γ, and CXCL10/IP10 may be candidates to detect and monitor disease status.
authors.affiliation: Department of Hygiene, Kawasaki Medical School, Okayama, Japan. mmaeda@cc.okayama-u.ac.jp
authors.forename: Megumi
authors.initials: M
authors.lastname: Maeda
authors.forename: Yasumitsu
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Naoko
authors.initials: N
authors.lastname: Kumagai
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Shuko
authors.initials: S
authors.lastname: Murakami
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Miura
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Hiratsuka
authors.forename: Takumi
authors.initials: T
authors.lastname: Kishimoto
authors.forename: Takemi
authors.initials: T
authors.lastname: Otsuki
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D017632:Asbestos, Serpentine / Q000633:toxicity*; D001195:Asbestosis / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D054357:Chemokine CXCL10 / Q000097:blood; D003252:Construction Materials / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D008654:Mesothelioma / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000378:metabolism*; D013997:Time Factors; D019139:Tumor Escape / Q000187:drug effects*
chemical_list: D017632:Asbestos, Serpentine; C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D007371:Interferon-gamma