Enhancement of regulatory T cell-like suppressive function in MT-2 by long-term and low-dose exposure to asbestos

Our plain-English summary of Enhancement of regulatory T cell-like suppressive function in MT-2 by long-term and low-dose exposure to asbestos, by C. Ying, M. Maeda, Y. Nishimura, et al (Toxicology, 2015).

The study

• Authors: C. Ying, M. Maeda, Y. Nishimura, N. Kumagai-Takei, H. Hayashi, H. Matsuzaki, S. Lee, K. Yoshitome, S. Yamamoto, T. Hatayama, T. Otsuki
• Journal: Toxicology
• Published: 2015;338:86-94
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Asbestos exposure causes lung fibrosis and various malignant tumors such as lung cancer and malignant mesothelioma. The effects of asbestos on immune cells have not been thoroughly investigated, although our previous reports showed that asbestos exposure reduced anti-tumor immunity. The effects of continuous exposure of regulatory T cells (Treg) to asbestos were examined using the HTLV-1 immortalized human T cell line MT-2, which possesses a suppressive function and expresses the Treg marker protein, Foxp3. Sublines were generated by the continuous exposure to low doses of asbestos fibers for more than one year. The sublines exposed to asbestos showed enhanced suppressive Treg function via cell-cell contact, and increased production of soluble factors such as IL-10 and transforming growth factor (TGF)-β1. These results also indicated that asbestos exposure induced the reduction of anti-tumor immunity, and efforts to develop substances to reverse this reduction may be helpful in preventing the occurrence of asbestos-induced tumors.

Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

In plain English

This was a laboratory study of cells, not people. The authors used MT-2, a human T cell line that behaves like regulatory T cells (Treg), which restrain other immune cells. They grew six sublines in continuous low doses of chrysotile asbestos for more than eight months: three in chrysotile A (CA 1–3), three in chrysotile B (CB 1–3). They measured how strongly the cells slowed growth of responder T cells from healthy donors. All three CB sublines and CA 3 suppressed more than unexposed MT-2, significantly so for CB 1 and CB 3 at one cell ratio; CA 1 and CA 2 suppressed less. CB 1 suppressed more than unexposed MT-2 when responder cells were stimulated through dendritic cells, but not with antibodies alone. It also made more IL-10 and TGF-beta1; knocking these down reduced its suppression when the cells were kept apart. The authors attributed about half of CB 1's extra suppression to these factors and half to cell-to-cell contact. They concluded that asbestos-exposed Treg showed enhanced function and exposed individuals appeared to have reduced anti-tumor immunity.

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: Laboratory (in vitro) cell-line experiment: asbestos-exposed sublines of a human T cell line were compared with the unexposed original line
• Who was studied: The human HTLV-1 immortalized polyclonal T cell line MT-2, used as Treg-like cells, and six asbestos-exposed sublines. Responder T cells and other blood cells came from healthy donors at Kawasaki Medical School, Japan.
• Exposure: Continuous low-dose exposure to International Union Against Cancer standard chrysotile A or chrysotile B. The dose is printed as 10 mg/mL. The duration is given as more than eight months in the methods and more than one year in the introduction. The authors note that chrysotile A contains 2% fibrous anthophyllite and chrysotile B contains no fibrous impurities.
• Main results:
  • In the mixed lymphocyte reaction test, unexposed MT-2 and all six sublines strongly suppressed responder T cells. They fully blocked responder T cell growth at ratios of 1:4, 1:2 and 1:1.
  • CB 1–3 and CA 3 suppressed more strongly than unexposed MT-2. The difference was statistically significant for CB 1 and CB 3 at the 1:64 ratio (p = 0.0057 and p = 0.0015).
  • Sublines CA 1 and CA 2 suppressed less than unexposed MT-2.
  • When responder T cells were stimulated with antibodies, CB 1 and unexposed MT-2 suppressed with the same intensity.
  • When responder T cells were stimulated with antibody plus immature dendritic cells (described by the authors as stimulation via cell-to-cell contact), CB 1 suppressed more than unexposed MT-2. The difference was significant at ratios of 1:64 (p = 0.04) and 1:16 (p = 0.037).
  • The Treg markers Foxp3 and GITR were high in both unexposed MT-2 and CB 1–3, with no significant differences.
  • CTLA4 tended to increase slightly in CB 1–3, but the increase was significant only in CB 3.
  • CB 1 produced significantly more IL-10 and TGF-beta1 than unexposed MT-2.
  • In a test where the cells could not touch (transwell), about 45% of responder T cells did not divide with control CB 1. This fell to 15% with IL-10-knocked-down CB 1 and to 30% with TGF-beta1-knocked-down CB 1.
  • The authors interpreted these results as showing that about half of CB 1's enhanced suppression came from soluble factors and the rest from cell-to-cell contact.
• The authors' conclusion: The authors concluded that Treg-like cells continuously exposed to asbestos fibers showed enhanced function, through cell-to-cell contact and increased soluble factors. They also concluded that individuals exposed to asbestos appeared to have reduced anti-tumor immunity.
• Limitations the authors state:
  • The authors noted that the standard deviation in the mixed lymphocyte reaction results was relatively large.
  • The authors noted that studies of asbestos-exposed patients had not shown whether patients' circulating Treg have the enhanced function seen in this cell line model.
  • The authors did not measure CD103, a molecule they describe as important for contact-dependent Treg function.

Topics

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

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

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)
• 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)
• 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)
• 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)
• The Effects of Asbestos Fibers on Human T Cells — N. Kumagai-Takei, S. Lee, et al. (2020)
• Alteration of cytoskeletal molecules in a human T cell line caused by continuous exposure to chrysotile asbestos — M. Maeda, Y. Chen, et al. (2013)

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