Inflammatory Alteration of Human T Cells Exposed Continuously to Asbestos

Our plain-English summary of Inflammatory Alteration of Human T Cells Exposed Continuously to Asbestos, by N. Kumagai-Takei, S. Yamamoto, S. Lee, et al (International Journal of Molecular Sciences, 2018).

The study

• Authors: N. Kumagai-Takei, S. Yamamoto, S. Lee, M. Maeda, H. Masuzzaki, N. Sada, M. Yu, K. Yoshitome, Y. Nishimura, T. Otsuki
• Journal: International Journal of Molecular Sciences
• Published: 2018;19(2)
• Type of article: Review
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Asbestos is a known carcinogen and exposure can lead to lung cancer and malignant mesothelioma. To examine the effects of asbestos fibers on human immune cells, the human T cell leukemia/lymphoma virus (HTLV)-1 immortalized human T cell line MT-2 was employed. Following continuous exposure to asbestos fibers for more than eight months, MT-2 sublines showed acquisition of resistance to asbestos-induced apoptosis with decreased death signals and increased surviving signals. These sublines showed various characteristics that suggested a reduction in anti-tumor immunity. On the other hand, inflammatory changes such as expression of MMP7, CXCR5, CXCL13 and CD44 was found to be markedly higher in sublines continuously exposed to asbestos compared with original MT-2 cells. All of these molecules contribute to lung inflammation, T and B cell interactions and connections between mesothelial cells and T cells. Thus, further investigation focusing on these molecules may shed light on the role of chronic inflammation caused by asbestos exposure and the occurrence of malignant mesothelioma. Finally, regarding peripheral T cells from healthy donors (HD) and asbestos-exposed patients with pleural plaque (PP) or malignant pleural mesothelioma (MPM), following stimulation of CD4+ T cells, T cells from MPM patients showed reduced potential of interferon (IFN)-γ expression. Moreover, levels of interleukin (IL)-6, one of the most important cytokines in chronic inflammation, in cultured supernatants were higher in PP and MPM patients compared with HD. Overall, asbestos-induced chronic inflammation in the lung as well as the pleural cavity may facilitate the onset of asbestos-induced cancers due to alterations in the interactions among fibers, immune cells such as T and B cells and macrophages, and mesothelial and lung epithelial cells. Further investigations regarding chronic inflammation caused by asbestos fibers may assist in identifying molecular targets for preventive and therapeutic strategies related to the effects of asbestos exposure.

In plain English

This brief review summarized the authors' own laboratory research on how long-term asbestos exposure affects human T cells, a type of immune cell. The work exposed the human T cell line MT-2 to relatively low doses of chrysotile A, chrysotile B or crocidolite for over eight months. All ten resulting sublines became resistant to asbestos-induced cell death, with reduced FoxO1 and increased IL-10 and Bcl-2. The sublines also showed reduced CXCR3, a molecule tied to anti-tumor immunity. In unpublished preliminary data, two sublines showed significantly higher MMP7, CXCR5, CXCL13 and CD44 than the original cells. In stimulated blood CD4+ T cells, IFN-γ mRNA was significantly lower in malignant pleural mesothelioma patients than in healthy donors or pleural plaque patients. IL-6 was higher in the culture fluid of stimulated CD4+ T cells from plaque and mesothelioma patients than from healthy donors. Earlier, their serum tests found significant IL-6 increases only in mesothelioma patients. The authors concluded that asbestos-related cancers may arise from chronic inflammation and altered immune-cell interactions. They said these findings needed further study, including in patient specimens.

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: Brief review of the authors' own previous laboratory studies (cell-line experiments and blood T cells from patients), including some unpublished preliminary data
• Who was studied: The human T cell line MT-2 (immortalized by HTLV-1) and ten sublines derived from it (three exposed to chrysotile B, three to chrysotile A, four to crocidolite). Also peripheral blood CD4+ T cells from healthy donors, patients with pleural plaque, and patients with malignant pleural mesothelioma. The number of donors and patients is not given.
• Exposure: Continuous, relatively low-dose exposure of MT-2 cells to chrysotile A, chrysotile B or crocidolite for more than eight months. The doses were set below those that drove half of the cells into apoptosis after short-term exposure.
• Main results:
  • All continuously exposed MT-2 sublines acquired resistance to asbestos-induced apoptosis (cell death).
  • In all continuously exposed sublines, the death signal was reduced: expression of the transcription factor FoxO1 fell drastically.
  • In all sublines, survival signals were increased: IL-10 secretion rose, and Bcl-2 was up-regulated.
  • CXCR3 expression was reduced in the sublines. It was also reduced in peripheral CD4 positive T cells from pleural plaque and malignant pleural mesothelioma patients.
  • In unpublished preliminary data, the CB1 subline (chrysotile B) and the CR1 subline (crocidolite) had significantly higher expression of MMP7, CXCR5, CXCL13 and CD44 than original MT-2 cells (p less than 0.05).
  • After five days of stimulation, IFN-γ mRNA expression was significantly lower in CD4+ T cells from malignant pleural mesothelioma patients than in cells from healthy donors or pleural plaque patients.
  • IL-6 levels in the culture supernatants of stimulated CD4+ T cells were higher for pleural plaque and malignant pleural mesothelioma patients than for healthy donors. IFN-γ levels in the supernatants did not differ among the three groups.
  • In the authors' earlier serum measurements, IL-6 was significantly increased only in the serum of malignant pleural mesothelioma patients, not in pleural plaque patients or healthy donors.
• The authors' conclusion: The authors concluded that asbestos-induced cancers such as lung cancer and mesothelioma may be derived from chronic inflammation caused by asbestos exposure and from altered interactions among immune cells.
• Limitations the authors state:
  • The authors stated that the gene-expression results for MMP7, CXCR5, CXCL13 and CD44 were not yet published. They said further experiments, including studies of specimens from asbestos-exposed patients, are needed.

Topics

Medical terms in this study, explained in our Lexicon: Lung Cancer, Malignant Mesothelioma, Apoptosis, Inflammation, Mesothelial Cells, Chronic Inflammation, Asbestos Exposure, Pleural Plaques.

Related studies

• Aberrant expression of FoxP3 in a human T cell line possessing regulatory T cell‑like function and exposed continuously to asbestos fibers — M. Maeda, H. Matsuzaki, et al. (2018)
• Resistance to asbestos-induced apoptosis with continuous exposure to crocidolite on a human T cell — M. Maeda, S. Yamamoto, et al. (2012)
• Enhanced expression of nicotinamide nucleotide transhydrogenase (NNT) and its role in a human T cell line continuously exposed to asbestos — S. Yamamoto, S. Lee, et al. (2020)
• Asbestos-induced cellular and molecular alteration of immunocompetent cells and their relationship with chronic inflammation and carcinogenesis — H. Matsuzaki, M. Maeda, et al. (2012)
• FoxO1 regulates apoptosis induced by asbestos in the MT-2 human T-cell line — H. Matsuzaki, S. Lee, et al. (2016)
• Reduction of CXC chemokine receptor 3 in an in vitro model of continuous exposure to asbestos in a human T-cell line, MT-2 — M. Maeda, Y. Nishimura, et al. (2011)

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