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

Megumi Maeda, Yasumitsu Nishimura, Hiroaki Hayashi, Naoko Kumagai, Ying Chen, Shuko Murakami, Yoshie Miura, Jun Ichi Hiratsuka, Takumi Kishimoto, Takemi Otsuki

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 frompatients 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.

Original languageEnglish
Pages (from-to)795-803
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume45
Issue number4
DOIs
Publication statusPublished - Oct 1 2011

Keywords

  • Asbestos
  • CXCR3
  • IFN-γ
  • Malignant mesothelioma
  • Pleural plaque

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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    Maeda, M., Nishimura, Y., Hayashi, H., Kumagai, N., Chen, Y., Murakami, S., Miura, Y., Hiratsuka, J. I., Kishimoto, T., & Otsuki, T. (2011). Decreased CXCR3 expression in CD4 + T cells exposed to asbestos or derived from asbestos-exposed patients. American journal of respiratory cell and molecular biology, 45(4), 795-803. https://doi.org/10.1165/rcmb.2010-0435OC