Effect of asbestos exposure on differentiation and function of cytotoxic T lymphocytes

Our plain-English summary of Effect of asbestos exposure on differentiation and function of cytotoxic T lymphocytes, by N. Kumagai-Takei, Y. Nishimura, M. Maeda, et al (Environmental Health and Preventive Medicine, 2020).

The study

• Authors: N. Kumagai-Takei, Y. Nishimura, M. Maeda, H. Hayashi, H. Matsuzaki, S. Lee, K. Yoshitome, T. Ito, T. Otsuki
• Journal: Environmental Health and Preventive Medicine
• Published: 2020;25(1):59
• Type of article: Review
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Asbestos exposure is known to cause malignant mesothelioma, which is associated with poor prognosis. We focused on and examined the effect of asbestos exposure on the differentiation and function of cytotoxic T lymphocytes (CTLs). CTLs have the ability to specifically attack tumor cells after being differentiated from naïve CD8+ T cells following antigen stimulation. Exposure to chrysotile B asbestos suppressed the differentiation of CTLs during the mixed lymphocyte reaction (MLR) and was associated with a decrease in proliferation of CD8+ T cells. Additionally, in an effort to investigate the mechanism associated with suppressed CTL differentiation upon exposure to asbestos, we focused on IL-2, a cytokine involved in T cell proliferation. Our findings indicated that insufficient levels of IL-2 are not the main cause for the suppressed induction of CTLs by asbestos exposure, although they suggest potential improvement in the suppressed CTL function. Furthermore, the functional properties of peripheral blood CD8+ lymphocytes from asbestos-exposed individuals with pleural plaque (PP) and patients with malignant mesothelioma (MM) were examined. MM patients showed lower perforin levels in CD8+ lymphocytes following stimulation compared with PP-positive individuals. The production capacity of IFN-γ in the MM group tended to be lower compared with healthy volunteers or PP-positive individuals. In an effort to determine whether chronic and direct asbestos exposure affected the function of CD8+ T cells, cultured human CD8+ T cells were employed as an in vitro model and subjected to long-term exposure to chrysotile (CH) asbestos. This resulted in decreased levels of intracellular perforin and secreted IFN-γ. Those findings underlie the possibility that impaired CD8+ lymphocyte function is caused by asbestos exposure, which fail to suppress the development of MM. Our studies therefore reveal novel effects of asbestos exposure on CTLs, which might contribute towards the development and implementation of an effective strategy for the prevention and cure of malignant mesothelioma.

In plain English

This article is a review in which the authors summarized their own earlier laboratory studies on how asbestos affects cytotoxic T lymphocytes (CTLs), immune cells that can attack tumor cells. In stimulated human blood-cell cultures, chrysotile B asbestos at 5 μg/ml reduced the cells' ability to kill target cells. It also suppressed CTL development and CD8+ T cell growth and lowered IFN-γ and TNF-α production. Crocidolite did not reduce killing ability. Adding IL-2 partly restored some functions but not cell growth. The authors also compared blood from asbestos-exposed people with pleural plaques, patients with malignant mesothelioma, and healthy volunteers. Both asbestos-exposed groups had fewer CD8+ T cells per mL of blood than the volunteers. The mesothelioma patients had significantly lower perforin after stimulation than people with plaques. Their IFN-γ tended to be lower, but the difference was not statistically significant. A CD8+ T cell line cultured with chrysotile for 1 to 2 months showed lower perforin and lower secreted IFN-γ. The authors concluded that asbestos has the potential to suppress CTL differentiation and function. They noted that immune suppression coming from the tumor may also affect patients' cells.

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 previously published laboratory (in vitro) and blood-sample studies
• Who was studied: Human peripheral blood mononuclear cells in culture; blood CD8+ lymphocytes from asbestos-exposed individuals with pleural plaque, patients with malignant mesothelioma, and healthy volunteers (numbers not given in this review); and the human CD8+ T cell line EBT-8
• Exposure: Chrysotile B or crocidolite asbestos at 5 μg/ml during a 7-day mixed lymphocyte reaction; long-term chrysotile exposure of a CD8+ T cell line at 5 or 30 μg/ml for 1 to 2 months
• Main results:
  • In blood-cell cultures, chrysotile B exposure lowered cytotoxicity against allogenic targets; crocidolite exposure did not
  • Chrysotile B suppressed the increase in effector/memory (CD45RO+) and activated (CD25+) CD8+ cells, which the authors describe as suppressed differentiation into CTLs
  • Chrysotile B suppressed proliferation of CD8+ T cells, without an increase in apoptosis
  • In cultures exposed to chrysotile B, production of IFN-γ and TNF-α decreased, but production of IL-2 did not
  • Adding IL-2 (1 ng/mL) did not restore proliferation or CD25+ and CD45RO+ cells, but partially restored granzyme B+ cells and improved cytotoxicity
  • The number of CD3+CD8+ cells per 1 mL of blood was significantly lower in the pleural plaque and mesothelioma groups than in healthy volunteers
  • Degranulation (CD107a) of stimulated CD8+ lymphocytes did not differ among the three groups
  • IFN-γ production in the mesothelioma group tended to be lower than in healthy volunteers and the pleural plaque group, but the difference was not statistically significant
  • The mesothelioma group showed significantly lower perforin levels in CD8+ lymphocytes after stimulation than pleural plaque individuals
  • The percentage of perforin+ cells and CD45RA− cells in circulating CD8+ lymphocytes was higher in both the pleural plaque and mesothelioma groups than in healthy volunteers
  • In the CD8+ T cell line, long-term chrysotile exposure at both 5 and 30 μg/ml decreased perforin levels and had no effect on granzyme B levels
  • In the CD8+ T cell line, chrysotile at 30 μg/ml decreased secreted IFN-γ after stimulation via CD3, and degranulation was unaffected
• The authors' conclusion: The authors concluded that exposure to asbestos has the potential to suppress the differentiation and function of human CTLs. They suggested it is possible that asbestos-impaired CD8+ lymphocyte function results in failure to suppress the development of malignant mesothelioma.
• Limitations the authors state:
  • The authors note that the characteristics of CD8+ T cells in mesothelioma patients might be affected by immunosuppression derived from the tumor, rather than by asbestos

Topics

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

Medical terms in this study, explained in our Lexicon: Asbestos Exposure, Malignant Mesothelioma, Prognosis, Chrysotile, Cytokine, Pleural Plaques.

Related studies

• The Suppressed Induction of Human Mature Cytotoxic T Lymphocytes Caused by Asbestos Is Not due to Interleukin-2 Insufficiency — N. Kumagai-Takei, Y. Nishimura, et al. (2016)
• Functional Alteration of Natural Killer Cells and Cytotoxic T Lymphocytes upon Asbestos Exposure and in Malignant Mesothelioma Patients — Y. Nishimura, N. Kumagai-Takei, et al. (2015)
• 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)
• A 5-aza-2'-deoxycytidine/valproate combination induces cytotoxic T-cell response against mesothelioma — S. Leclercq, F. Gueugnon, et al. (2011)
• Chronic exposure to asbestos enhances TGF-β1 production in the human adult T cell leukemia virus-immortalized T cell line MT-2 — M. Maeda, Y. Chen, et al. (2014)
• Functional properties of CD8(+) lymphocytes in patients with pleural plaque and malignant mesothelioma — N. Kumagai-Takei, Y. Nishimura, et al. (2014)

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