Decreased CXCR3 expression in CD4+ T cells exposed to asbestos or derived from asbestos-exposed patients

• Published in: American journal of respiratory cell and molecular biology Vol. 45; no. 4; pp. 795 - 803
• Main Authors: Maeda, Megumi, Nishimura, Yasumitsu, Hayashi, Hiroaki, Kumagai, Naoko, Chen, Ying, Murakami, Shuko, Miura, Yoshie, Hiratsuka, Jun-ichi, Kishimoto, Takumi, Otsuki, Takemi
• Format: Journal Article
• Language: English
• Published: United States 01.10.2011
• Subjects: Adult; Apoptosis - drug effects; Asbestos, Serpentine - toxicity; Asbestosis - etiology; Asbestosis - genetics; Asbestosis - immunology; Asbestosis - pathology; Case-Control Studies; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; Cell Line, Tumor; Chemokine CXCL10 - blood; Construction Materials - toxicity; Dose-Response Relationship, Drug; Down-Regulation; Female; Humans; Interferon-gamma - genetics; Interferon-gamma - metabolism; Lung Neoplasms - chemically induced; Lung Neoplasms - genetics; Lung Neoplasms - immunology; Lung Neoplasms - pathology; Male; Mesothelioma - chemically induced; Mesothelioma - genetics; Mesothelioma - immunology; Mesothelioma - pathology; Middle Aged; Receptors, CXCR3 - metabolism; RNA, Messenger - metabolism; Time Factors; Tumor Escape - drug effects
• ISSN: 1044-1549; 1535-4989
• DOI: 10.1165/rcmb.2010-0435OC

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.