Functional Alteration of Natural Killer Cells and Cytotoxic T Lymphocytes upon Asbestos Exposure and in Malignant Mesothelioma Patients

Our plain-English summary of Functional Alteration of Natural Killer Cells and Cytotoxic T Lymphocytes upon Asbestos Exposure and in Malignant Mesothelioma Patients, by Y. Nishimura, N. Kumagai-Takei, H. Matsuzaki, et al (BioMed Research International, 2015).

The study

• Authors: Y. Nishimura, N. Kumagai-Takei, H. Matsuzaki, S. Lee, M. Maeda, T. Kishimoto, K. Fukuoka, T. Nakano, T. Otsuki
• Journal: BioMed Research International
• Published: 2015;2015:238431
• Type of article: Review
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma is caused by exposure to asbestos, which is known to have carcinogenic effects. However, the development of mesothelioma takes a long period and results from a low or intermediate dose of exposure. These findings have motivated us to investigate the immunological effects of asbestos exposure and analyze immune functions of patients with mesothelioma and pleural plaque, a sign of exposure to asbestos. Here, we review our knowledge concerning natural killer (NK) cells and cytotoxic T lymphocytes (CTL). NK cells showed impaired cytotoxicity with altered expression of activating receptors upon exposure to asbestos, while induction of granzyme(+) cells in CD8(+) lymphocytes was suppressed by asbestos exposure. It is interesting that a decrease in NKp46, a representative activating receptor, is common between NK cells in PBMC culture with asbestos and those of mesothelioma patients. Moreover, it was observed that CD8(+) lymphocytes may be stimulated by some kind of "nonself" cells in plaque-positive individuals and in mesothelioma patients, whereas CTL in mesothelioma is impaired by poststimulation maintenance of cytotoxicity. These findings suggest that analysis of immunological parameters might contribute to the evaluation of health conditions of asbestos-exposed individuals and to a greater understanding of the pathology of malignant mesothelioma.

In plain English

This review summarized a Japanese research group's own earlier laboratory and blood studies on how asbestos may affect two kinds of killer immune cells: natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). An NK cell line kept with chrysotile asbestos showed impaired killing ability after around 5 months. In blood, NK cells from 7 malignant mesothelioma patients had less of a surface receptor called NKp46 than those from 10 healthy people. Human blood cells cultured with chrysotile showed the same drop; glass wool did not cause it. Chrysotile also held back the development of killer function in CD8+ T cells in culture. Compared with 16 healthy volunteers, 16 people with pleural plaques and 14 mesothelioma patients had a higher percentage of CD8+ cells containing perforin, a cell-killing protein. After stimulation, this percentage fell in mesothelioma patients, while most healthy and plaque-positive individuals kept these cells. The authors concluded that asbestos exposure has the potential to suppress NK cell and CTL function. They said more studies were needed to tell whether CTL impairment in mesothelioma stems from the tumor or from asbestos.

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 studies (cell-line experiments, cell-culture experiments, and blood tests of patients and exposed individuals)
• Who was studied: A human NK cell line (YT-A1); human blood cells (PBMCs) in culture; peripheral blood NK cells from 7 malignant mesothelioma patients compared with 10 healthy individuals; and CD8+ lymphocytes from 16 individuals positive for pleural plaque and 14 mesothelioma patients compared with 16 healthy volunteers
• Exposure: In the laboratory: chrysotile B asbestos at 5 micrograms per millilitre, given to an NK cell line continuously and to blood cell cultures for 7 days. Glass wool, a man-made mineral fiber, was used for comparison. In people: pleural plaque, which the authors treat as a sign of past asbestos inhalation. Table 1 also lists earlier T helper cell work with crocidolite.
• Main results:
  • The NK cell line continuously exposed to chrysotile kept normal killing ability for the first month but showed impaired killing after around 5 months. It also had lower surface levels of the activating receptors NKG2D and 2B4.
  • Peripheral blood NK cells from 7 mesothelioma patients had lower killing ability and lower surface NKp46 than those of 10 healthy individuals. NKG2D and 2B4 were not lower.
  • NK cells in blood cell cultures exposed to chrysotile showed lower NKp46, while NKG2D and 2B4 did not differ from control cultures. Glass wool did not cause this change.
  • In a mixed lymphocyte reaction (a laboratory method for developing killer T cells), chrysotile exposure held back the increase in CD8+ lymphocyte numbers. The CD8+ cells from exposed cultures killed target cells less well than cells from control cultures.
  • Both the plaque-positive individuals and the mesothelioma patients had higher percentages of perforin-positive CD8+ cells than healthy volunteers. After stimulation, perforin-positive cells decreased in mesothelioma patients, whereas most healthy and plaque-positive individuals retained them.
• The authors' conclusion: The authors concluded that asbestos exposure has the potential to suppress the function of NK cells and CTLs. They also suggested that immune measures such as NKp46 expression might help evaluate the health of asbestos-exposed individuals.
• Limitations the authors state:
  • The authors said further studies are needed to determine whether the impaired CTL function in mesothelioma is caused by the tumor itself or by asbestos exposure before the tumor developed.
  • The authors noted that healthy and plaque-positive individuals cannot be compared in the same way as control and asbestos-exposed laboratory cultures.

Topics

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

Medical terms in this study, explained in our Lexicon: Asbestos Exposure, Malignant Mesothelioma, Carcinogenic, Mesothelioma, Pleural Plaques, Pathology.

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)
• Effect of asbestos exposure on differentiation and function of cytotoxic T lymphocytes — N. Kumagai-Takei, Y. Nishimura, et al. (2020)
• Lymphocyte subsets in subjects exposed to asbestos: changes in circulating natural killer cells — N. al Jarad, M. Macey, et al. (1992)
• Functional properties of CD8(+) lymphocytes in patients with pleural plaque and malignant mesothelioma — N. Kumagai-Takei, Y. Nishimura, et al. (2014)
• Asbestos and cancer: human natural killer cell activity is suppressed by asbestos fibers but can be restored by recombinant interleukin-2 — B.W. Robinson (1989)
• Natural killer cell activity in asbestos workers. Interactive effects of smoking and asbestos exposure — R.D. deShazo, J. Morgan, et al. (1988)

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