Polyclonal human T-cell activation by silicate in vitro

Our plain-English summary of Polyclonal human T-cell activation by silicate in vitro, by A. Ueki, M. Yamaguchi, H. Ueki, et al (Immunology, 1994).

The study

• Authors: A. Ueki, M. Yamaguchi, H. Ueki, Y. Watanabe, G. Ohsawa, K. Kinugawa, Y. Kawakami, F. Hyodoh
• Journal: Immunology
• Published: 1994;82(2):332-5
• Cited by: 78 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Silica (SiO2) or related substances such as silicone ([-R2Si-O-]n), which is used in plastic surgery, or asbestos (e.g. chrysotile; 3MgO.2SiO2.H2O) have 'adjuvant effects'. In a study of scleroderma patients in Germany more than 78% had experienced exposure to silicate dust. T-cell receptor (TcR) V beta gene analysis on CD4- CD8- double-negative alpha beta T cells from scleroderma patients, using polymerase chain reaction (PCR), showed that certain V beta genes, V beta 5, V beta 7 and V beta 17, were predominantly expressed in the cells. We found that certain V beta repertoires, V beta 5.3 and V beta 6.7, were predominantly expressed on fractionated T cells with a high Ca2+ level that had been stimulated by chrysotile in vitro. The intracellular Ca2+ level in human peripheral blood mononuclear cells (PBMC) increased after incubation with silica or chrysotile. Interleukin-2 (IL-2) release from PMBC also rose significantly with chrysotile stimulation, but no change was observed when major histocompatibility complex (MHC) class II DP/DR positive cells were depleted. Therefore, our results support the possibility that silicate acts as a superantigen.

In plain English

This laboratory study exposed blood cells from healthy volunteers to chrysotile asbestos, and in some tests to silica particles. After 6 days with chrysotile, total cell numbers rose without any change in viability. The share of CD4+ cells rose significantly (P less than 0.01), CD3+ cells did not rise, and CD19+ cells fell as the chrysotile dose rose (P less than 0.05). Lymphocyte calcium levels rose within minutes of exposure to silica or chrysotile. In three donors, chrysotile-stimulated cells with raised calcium showed about three times higher expression of one T-cell receptor type than others (V beta 6.7 in one donor, V beta 5.3 in two). A control test with the standard stimulant PHA, done on one donor's cells, did not show this. IL-2 release was significantly higher with chrysotile (P less than 0.05), but not after cells carrying HLA DP/DR markers were removed. The authors concluded that silicate acts on human lymphocytes as a superantigen, which they said seems to play an important role in scleroderma, Sjögren's syndrome and lupus in patients with silicosis or asbestosis.

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: in vitro laboratory experiment on human blood cells (published as a rapid communication)
• Who was studied: Peripheral blood mononuclear cells from healthy volunteers (n = 10 for the 6-day cell experiments, n = 5 for the IL-2 assay, and three donors for the T-cell receptor analysis: a 28-year-old male and two 24-year-old females)
• Exposure: Chrysotile (international standard reference sample) in culture, mainly at 50-100 micrograms per ml (100 micrograms per ml in the receptor and IL-2 tests), and silica particles in the calcium tests
• Main results:
  • After 6 days with chrysotile, the total cell number increased with no change in cell viability and no cytotoxicity at the doses used
  • The percentage of CD4+ cells increased significantly after 6 days (P less than 0.01), with no increase in CD3+ cells
  • CD19+ cells decreased in a dose-dependent way with the chrysotile concentration (P less than 0.05)
  • Intracellular calcium in lymphocytes rose after 1-10 minutes of incubation with silica or chrysotile and was still detectable after 30 minutes
  • In the three donors, chrysotile-stimulated cells with high calcium showed about three times higher expression of one specific T-cell receptor V beta type: V beta 6.7 in case I and V beta 5.3 in cases II and III
  • The PHA control was tested on part of the specimen from case I only, and the predominant receptor increase was not seen with PHA
  • IL-2 release was significantly higher in cells incubated with chrysotile than in controls (P less than 0.05, n = 5)
  • After removal of HLA DP/DR (MHC class II) expressing cells, chrysotile made no difference to IL-2 secretion
  • The number of IL-2 receptor positive cells increased with chrysotile (P less than 0.05), mainly among CD4+ cells and not CD8+ cells (data not shown)
• The authors' conclusion: The authors concluded that silicate acts on human lymphocytes as a superantigen, which they said seems to play an important role in scleroderma, Sjögren's syndrome and SLE in patients with silicosis or asbestosis
• Limitations the authors state:
  • Not all T-cell receptor types could be tested because of the limited number of antibodies available, and these need further study
  • The increase in receptor types was not restricted to one type

Topics

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

Medical terms in this study, explained in our Lexicon: Silicate, Chrysotile.

Related studies

• Activation of human CD4+CD45RA+ T cells by chrysotile asbestos in vitro — K. Kinugawa, A. Ueki, et al. (1992)
• Activation-induced cell death in human peripheral blood lymphocytes after stimulation with silicate in vitro — T. Aikoh, A. Tomokuni, et al. (1998)
• Biological effects of asbestos fibers on human cells in vitro--especially on lymphocytes and neutrophils — A. Ueki (2001)
• Inhibitory effects of anti-oxidants on apoptosis of a human polyclonal T-cell line, MT-2, induced by an asbestos, chrysotile-A — F. Hyodoh, A. Takata-Tomokuni, et al. (2005)
• Heterogeneity in immunologic functions of rat alveolar macrophages--their accessory cell function and IL-1 production — Y. Oghiso (1987)
• Mineral fiber-induced leukocyte activation: the role of intra- and extracellular calcium — M. Ruotsalainen, J. Naarala, et al. (1995)

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