Reduction of CXC chemokine receptor 3 in an in vitro model of continuous exposure to asbestos in a human T-cell line, MT-2

Our plain-English summary of Reduction of CXC chemokine receptor 3 in an in vitro model of continuous exposure to asbestos in a human T-cell line, MT-2, by M. Maeda, Y. Nishimura, H. Hayashi, et al (American Journal of Respiratory Cell and Molecular Biology, 2011).

The study

• Authors: M. Maeda, Y. Nishimura, H. Hayashi, N. Kumagai, Y. Chen, S. Murakami, Y. Miura, J. Hiratsuka, T. Kishimoto, T. Otsuki
• Journal: American Journal of Respiratory Cell and Molecular Biology
• Published: 2011;45(3):470-9
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Because patients with silicosis who are chronically exposed to silica particles develop not only pulmonary fibrosis, but also complications involving autoimmune diseases such as rheumatoid arthritis and systemic sclerosis, exposure to asbestos may affect the human immune system. This immunologic effect may impair antitumor immune function because cancer complications such as lung cancer and malignant mesothelioma are found in patients exposed to asbestos. To elucidate the antitumor immune status caused by CD4(+) T cells exposed to asbestos, an in vitro T-cell model of long-term and low-level exposure to chrysotile asbestos was established from a human adult T-cell leukemia virus-1-immortalized human polyclonal T cell line, MT-2, and the resulting six sublines showed resistance to asbestos-induced apoptosis after more than 8 months of continuous exposure. The results of DNA microarray analysis showed that the expression of 139 genes was altered by long-term and low-level exposure to asbestos, and the profile was almost similar among the six sublines when compared with the original MT-2 cells that had never been exposed to asbestos. Pathway and network analysis indicated a down-regulation of IFN-γ signaling and expression of CXC chemokine receptor 3 (CXCR3) in the sublines, whereas ELISA and flow cytometry analysis demonstrated a reduction in Th1-related IFN-γ production and cell-surface CXCR3 expression. These findings suggest that chronic exposure to asbestos may reduce antitumor immune status in CD4(+) T cells, and that an in vitro T-cell model may be useful in identifying molecules related to the impairment of antitumor immune function.

In plain English

This was a laboratory study of a human immune-cell line called MT-2, a type of T cell made to keep dividing in culture by the HTLV-1 virus. No people were studied. The authors grew six separate batches (sublines) of these cells with low levels of chrysotile asbestos for 8 to 12 months. Three got chrysotile-A from Zimbabwe, which contains 2% fibrous anthophyllite, and three got chrysotile-B from Canada. By then the sublines had become resistant to asbestos-induced cell death. Compared with the original, never-exposed cells, 139 genes changed activity more than twofold (84 up, 55 down), in a similar pattern in all six sublines. All sublines had fewer cells carrying the CXCR3 receptor on their surface, although CXCR3 gene activity in one subline (CB2) did not differ significantly from the original cells. All sublines also made less of the immune signals IFN-γ and CXCL10/IP10. The authors concluded that chronic asbestos exposure may reduce anti-tumor immune activity in this type of T cell. They said this should be checked in fresh blood cells from healthy donors and mesothelioma patients.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: In vitro laboratory experiment: long-term, low-level asbestos exposure of a human T-cell line, with gene-expression (DNA microarray), pathway and network analysis, flow cytometry, ELISA and real-time RT-PCR
• Who was studied: Cultured cells, not people: the HTLV-1-immortalized human polyclonal T-cell line MT-2 (original, never-exposed cells) compared with six independent asbestos-exposed, apoptosis-resistant sublines (CA1 to CA3 and CB1 to CB3). Work was done at Kawasaki Medical School and collaborating institutions in Japan. No dates are given.
• Exposure: Continuous low-level exposure to UICC standard chrysotile asbestos for 8 to 12 months. Chrysotile-A (from Zimbabwe, containing 2% fibrous anthophyllite) was used for three sublines and chrysotile-B (from Canada, no fibrous impurities) for three. Cultures started at 2 mg/cm2 as printed, a dose that halved growth of the original cells.
• Main results:
  • After 8 to 12 months of culture with chrysotile-A or chrysotile-B, the exposed sublines showed a reduced fraction of cells undergoing asbestos-induced cell death (apoptosis).
  • Compared with the original MT-2 cells, 139 genes were significantly altered by more than twofold in the exposed sublines: 84 up-regulated and 55 down-regulated.
  • The gene expression pattern was similar among all six exposed sublines, with small differences.
  • Pathway analysis found reduced expression of IRF9 and ISGF3, two genes in the IFN-γ signaling pathway, in all exposed sublines.
  • All exposed sublines showed fewer cells with CXCR3 on their surface. By real-time RT-PCR, the CB2 subline did not differ significantly from the original cells.
  • All exposed sublines produced less IFN-γ than the original MT-2 cells (measured by ELISA).
  • Production of CXCL10/IP10 was significantly reduced in all exposed sublines compared with the original cells.
  • CCL4/MIP-1b mRNA was lower in all exposed sublines, but CCR5 mRNA was not significantly reduced.
• The authors' conclusion: The authors concluded that chronic exposure to asbestos may reduce antitumor immune status in CD4+ T cells, and that this in vitro T-cell model may be useful for identifying molecules involved.
• Limitations the authors state:
  • The findings come from cell-line models and need to be confirmed in freshly isolated lymphocytes from healthy donors and from patients with mesothelioma exposed to asbestos.

Topics

Medical terms in this study, explained in our Lexicon: Silicosis, Pulmonary Fibrosis, Lung Cancer, Mesothelioma, Chrysotile, Apoptosis.

Related studies

• Decreased CXCR3 expression in CD4+ T cells exposed to asbestos or derived from asbestos-exposed patients — M. Maeda, Y. Nishimura, et al. (2011)
• Alteration of cytoskeletal molecules in a human T cell line caused by continuous exposure to chrysotile asbestos — M. Maeda, Y. Chen, et al. (2013)
• Accelerated cell cycle progression of human regulatory T cell-like cell line caused by continuous exposure to asbestos fibers — S. Lee, H. Matsuzaki, et al. (2017)
• Resistance to asbestos-induced apoptosis with continuous exposure to crocidolite on a human T cell — M. Maeda, S. Yamamoto, et al. (2012)
• FoxO1 regulates apoptosis induced by asbestos in the MT-2 human T-cell line — H. Matsuzaki, S. Lee, et al. (2016)
• Decrease in phosphorylation of ERK following decreased expression of NK cell-activating receptors in human NK cell line exposed to asbestos — Y. Nishimura, M. Maeda, et al. (2009)

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