AI Article Synopsis
- Asbestos exposure is linked to the development of mesothelioma and reduces the immune system's ability to produce cytotoxic T lymphocytes (CTLs), crucial for fighting tumors.
- In experiments, adding interleukin-15 (IL-15) to cultured immune cells exposed to asbestos partly restored the number of active CD8 T cells and increased granzyme B, a protein important for tumor cell destruction.
- However, IL-15 did not reverse all the negative effects of asbestos, particularly regarding certain markers (CD25 and CD45RO) in CD8 lymphocytes, indicating a complex interaction between asbestos exposure and immune response.
Article Abstract
Background: Asbestos fibers possess tumorigenicity and are thought to cause mesothelioma. We have previously reported that exposure to asbestos fibers causes a reduction in antitumor immunity. Asbestos exposure in the mixed lymphocyte reaction (MLR) showed suppressed induction of cytotoxic T lymphocytes (CTLs), accompanied by a decrease in proliferation of CD8 T cells. Recently, we reported that asbestos-induced suppression of CTL induction is not due to insufficient levels of interleukin-2 (IL-2). In this study, we continue to investigate the mechanism responsible for the effect of asbestos fibers on the differentiation of CTLs and focus on interleukin-15 (IL-15) which is known to be a regulator of T lymphocyte proliferation.
Methods: For MLR, human peripheral blood mononuclear cells (PBMCs) were cultured with irradiated allogenic PBMCs upon exposure to chrysotile B asbestos at 5 μg/ml for 7 days. After 2 days of culture, IL-15 was added at 1 ng/ml. After 7 days of MLR, PBMCs were collected and analyzed for phenotypic and functional markers of CD8 T cells with fluorescence-labeled anti-CD3, anti-CD8, anti-CD45RA, anti-CD45RO, anti-CD25, and anti-granzyme B antibodies using flow cytometry. To examine the effect of IL-15 on the expression level of intracellular granzyme B in proliferating and non-proliferating CD8 lymphocytes, PBMCs were stained using carboxyfluorescein diacetate succinimidyl ester (CFSE) and then washed and used for the MLR.
Results: IL-15 addition partially reversed the decrease in CD3CD8 cell numbers and facilitated complete recovery of granzyme B cell percentages. IL-15 completely reversed the asbestos-induced decrease in percentage of granzyme B cells in both non-proliferating CFSE-positive and proliferating CFSE-negative CD8 cells. The asbestos-induced decrease in the percentage of CD25 and CD45RO cells in CD8 lymphocytes was not reversed by IL-15.
Conclusion: These findings indicate that CTLs induced upon exposure to asbestos possess dysfunctional machinery that can be partly compensated by IL-15 supplementation, and that IL-15 is more effective in the recovery of proliferation and granzyme B levels from asbestos-induced suppression of CTL induction compared with IL-2.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056682 | PMC |
| http://dx.doi.org/10.1186/s12199-021-00967-9 | DOI Listing |
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Article Synopsis
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