The Effects of Asbestos Fibers on Human T Cells

Our plain-English summary of The Effects of Asbestos Fibers on Human T Cells, by N. Kumagai-Takei, S. Lee, B. Srinivas, et al (International Journal of Molecular Sciences, 2020).

The study

• Authors: N. Kumagai-Takei, S. Lee, B. Srinivas, Y. Shimizu, N. Sada, K. Yoshitome, T. Ito, Y. Nishimura, T. Otsuki
• Journal: International Journal of Molecular Sciences
• Published: 2020;21(19)
• Type of article: Review
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Asbestos exposure causes malignant tumors such as lung cancer and malignant mesothelioma. The effects of asbestos fibers on immunocompetent cells, however, have not been well studied. Asbestos physically comprises a fibrous substance, which differs from silica particles which are a particulate substance, although chemically it is a mineral silicate. Since silicosis patients previously exposed to silica particles often suffer from lung and autoimmune diseases, it is clear that silica exposure impairs immune tolerance. Similarly, asbestos may alter the immune system in asbestos-exposed individuals. Given that malignant tumors can result following exposure to asbestos, the attenuation of anti-tumor immunity in cases of asbestos exposure is an important area of investigation. We observed the effect of asbestos fibers on T lymphocytes, such as CD8+ cytotoxic T lymphocytes (CTLs), CD4+ helper T (Th), and regulatory T (Treg) cells, and showed that anti-tumor immunity was attenuated, as demonstrated in a system that stimulates fresh cells isolated from peripheral blood in vitro and a system that is continuously exposed to a cell line. In this manuscript, we introduce the experiments and results of studies on CTLs, as well as Th and Treg cells, and discuss how future changes in immunocompetent cells induced by asbestos fibers can be clinically linked.

In plain English

This article is a review in which the authors summarized their own laboratory's earlier studies of how asbestos fibers affect human T cells, immune cells involved in fighting tumors. The reviewed experiments used blood cells from healthy volunteers cultured with chrysotile, and human cell lines kept in long-term, relatively low-dose contact with chrysotile or crocidolite. They also used blood cells from people with pleural plaques or malignant mesothelioma. The article gives no numbers of patients or volunteers and no fiber doses. In the reviewed work, chrysotile suppressed the development of CD8+ killer T cells and reduced molecules they use to kill cells. Killing-related molecules in CD8+ cells were higher in plaque patients and lower in mesothelioma patients than in healthy volunteers. In helper T cells, chrysotile markedly changed the receptor CXCR3 and reduced interferon-gamma. In a regulatory T cell-like cell line, long-term exposure increased the cytokines IL-10 and TGF-beta and sped up the cell cycle. The authors concluded that the findings suggested asbestos exposure impaired anti-tumor immunity. They stated it was unclear whether reduced immunity in mesothelioma patients was a cause or a result of the disease.

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: Review of the authors' own previous laboratory studies (cell culture experiments and blood samples from patients)
• Who was studied: Blood cells from healthy volunteers. Human non-tumorous cell lines (EBT-8 for CD8+ T cells, MT-2 for regulatory T cells). Blood cells from patients with pleural plaque or malignant mesothelioma who had previously been exposed to asbestos. No numbers, locations or dates are given.
• Exposure: Mainly chrysotile in cell cultures. Chrysotile or crocidolite for the MT-2 sublines, at concentrations that caused cell death in less than half the cells with short exposure, then applied continuously over the long term. The patients' own past asbestos exposure is not described.
• Main results:
  • In healthy volunteers' blood cells, adding chrysotile suppressed the differentiation and multiplication of CD8+ killer T cells.
  • In the same experiments, the cytokines interferon-gamma and TNF-alpha, which are involved in cell killing, decreased with fiber exposure.
  • In stimulated CD8+ cells from patients, granzyme B and perforin levels were higher in pleural plaque patients and lower in malignant mesothelioma patients compared with healthy volunteers.
  • In the CD8+ cell line exposed to chrysotile for about two months, granzyme B showed no obvious change, but perforin and interferon-gamma production were reduced.
  • In helper (CD4+) T cells from healthy volunteers, chrysotile markedly changed expression of the receptor CXCR3 and reduced interferon-gamma.
  • In CD4+ cells from patients, interferon-gamma was lower in the malignant mesothelioma group but did not differ between healthy volunteers and the pleural plaque group.
  • IL-6 levels in cells from the pleural plaque and mesothelioma groups were higher than in healthy volunteers. The difference between the plaque and mesothelioma groups was not statistically significant.
  • In MT-2 sublines continuously exposed to asbestos, expression and production of IL-10 and TGF-beta, cytokines used by regulatory T cells, were markedly increased.
  • In the exposed MT-2 sublines, the transcription factor FoxO1 was significantly reduced and the cell cycle was accelerated.
  • NNT, an enzyme related to oxidative stress, was extremely high in the exposed MT-2 sublines.
  • Plasma IP-10 was higher in pleural plaque and mesothelioma patients than in healthy volunteers. In the mesothelioma group, CXCR3 expression and serum IP-10 showed a significant inverse correlation (p less than 0.05).
• The authors' conclusion: The authors concluded that their findings suggested continued exposure of T lymphocytes to asbestos fibers impaired anti-tumor immunity.
• Limitations the authors state:
  • It is unclear whether reduced anti-tumor immunity in mesothelioma patients is a cause or a result of the mesothelioma.
  • The pleural plaque patients could not recall the circumstances of their asbestos exposure.
  • Th17 cells have not yet been examined.
  • The molecular mechanisms behind the changes in regulatory T cells remain unknown.
  • The work focused on circulating immune cells. The immune environment at the sites where fibers remain was not addressed.
  • RANTES has not yet been measured.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Asbestos Exposure, Lung Cancer, Mesothelioma, Silicate, Silicosis.

Related studies

• Increased production of matrix metalloproteinase-7 (MMP-7) by asbestos exposure enhances tissue migration of human regulatory T-like cells — S. Lee, S. Yamamoto, et al. (2021)
• 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)
• 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)
• Decrease in Intracellular Perforin Levels and IFN-γ Production in Human CD8+ T Cell Line following Long-Term Exposure to Asbestos Fibers — N. Kumagai-Takei, Y. Nishimura, et al. (2018)
• Dual control of antitumor CD8 T cells through the programmed death-1/programmed death-ligand 1 pathway and immunosuppressive CD4 T cells: regulation and counterregulation — A.J. Currie, A. Prosser, et al. (2009)
• Enhancement of regulatory T cell-like suppressive function in MT-2 by long-term and low-dose exposure to asbestos — C. Ying, M. Maeda, et al. (2015)

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