Abstract
Although the tumorigenicity of asbestos, which is thought to cause mesothelioma, has been clarified, its effect on antitumor immunity requires further investigation. We previously reported a decrease in the percentage of perforin+ cells of stimulated CD8+ lymphocytes derived from patients with malignant mesothelioma. Therefore, we examined the effects of long-term exposure to asbestos on CD8+ T cell functions by comparing long-term cultures of the human CD8+ T cell line EBT-8 with and without exposure to chrysotile (CH) asbestos as an in vitro model. Exposure to CH asbestos at 5 μg/ml or 30 μg/ml did not result in a decrease in intracellular granzyme B in EBT-8 cells. In contrast, the percentage of perforin+ cells decreased at both doses of CH exposure. CH exposure at 30 μg/ml did not suppress degranulation following stimulation with antibodies to CD3. Secreted production of IFN-γ stimulated via CD3 decreased by CH exposure at 30 μg/ml, although the percentage of IFN-γ+ cells induced by PMA/ionomycin did not decrease. These results indicate that long-term exposure to asbestos can potentially suppress perforin levels and the production of IFN-γ in human CD8+ T cells.
Highlights
The association between mesothelioma and asbestos exposure is undisputed [1, 2]
We reported that patients with MM showed lower levels of perforin in CD8+ lymphocytes after stimulation compared to patients with pleural plaque (PP), and the percentage of IFN-γ+ cells in CD8+ lymphocytes of patients with MM tended to be lower compared to healthy volunteers (HV) and patients with PP [16]
The growth of EBT-8 cells was inhibited by exposure to a Union Against Cancer (UICC) standard sample of chrysotile asbestos at over 50 μg/ml (Figure 1(a))
Summary
The association between mesothelioma and asbestos exposure is undisputed [1, 2]. Previous studies have focused largely on the properties of asbestos fibers that are important in the development of MM and the mechanisms of action of asbestos in the multistage carcinogenic process [3,4,5,6]. The induction of malignant mesothelioma (MM) by exposure to asbestos is not a rapid process and takes a long period to develop [7,8,9]. This suggests the possibility that the development of MM might be related to other functional alterations and prompted us to suppose that exposure to inhaled asbestos might gradually impair the immune response. For an in vitro model representing continuous exposure to asbestos in a human CD4+ T cell line, MT-2 cells were subjected to long-term exposure to asbestos and showed a reduction in cell surface CXCR3 expression [11]. Those immunesuppressive characteristics of asbestos exposure were demonstrated by experiments with human primary cells, in which NK cells showed low expression of activating receptor
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