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

Authors :
Maeda M
Nishimura Y
Hayashi H
Kumagai N
Chen Y
Murakami S
Miura Y
Hiratsuka J
Kishimoto T
Otsuki T
Source :
American journal of respiratory cell and molecular biology [Am J Respir Cell Mol Biol] 2011 Oct; Vol. 45 (4), pp. 795-803. Date of Electronic Publication: 2011 Feb 25.
Publication Year :
2011

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.

Details

Language :
English
ISSN :
1535-4989
Volume :
45
Issue :
4
Database :
MEDLINE
Journal :
American journal of respiratory cell and molecular biology
Publication Type :
Academic Journal
Accession number :
21357438
Full Text :
https://doi.org/10.1165/rcmb.2010-0435OC