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Asbestos exposure can cause malignant mesothelioma and lung cancer. In the anti-tumor immune response, cytotoxic T lymphocytes (CTL) differentiated from naïve CD8+ T cells play a critical role. Therefore, we investigated the effect of asbestos exposure on induction of human CTL in mixed lymphocyte reactions (MLR). The functional property of CD8+ lymphocytes in peripheral blood mononuclear cells (PBMCs) of asbestos-exposed people with pleural plaque (PL) was also examined.
Methods
PBMCs were cultured with irradiated allogenic PBMCs with or without chrysotile B (CB) or crocidolite (CR) asbestos at 5 µg/ml. After 7 days of MLR, phenotypes of CD8+ cells, apoptosis, cell-proliferation, allogenic cytotoxicity and productions of cytokines were assayed by flow cytometry and Cytometric Beads Array. Freshly prepared PBMCs of healthy volunteers (HV) or people with PL were stimulated with PMA/ionomycin for 4h to examine the functions of CD8+ lymphocytes, assayed by flow cytometry.
Results
PBMCs exposed to CB, but not CR, showed a marked decrease in cytotoxicity. They also showed decreases in granzyme B+ cells, IFN-gamma+ cells, CD45RO+ effector/memory cells and CD25+ activated cells in CD8+ cells compared with PBMCs after MLR without CB. CB exposure suppressed the proliferation in CD8+ cells without increase in annexin V+ apoptotic cells in CD8+ and CD4+ cells. The productions of IL-10, IFN-gamma, and TNF-alpha, but not IL-2 were also suppressed by CB exposure. There was no difference in the percentage of IFN-gamma+ cells in stimulated CD8+ lymphocytes between PL group and HV. In contrast, the percentages of granzyme B+ and perforin+ cells were higher in PL group than HV.
Discussion
These suppressive effects of asbestos exposure on induction of CTL might promote the generation of tumor disease. The results obtained from specimens suggest that most of PL-positive people might have a paradoxically high cytotoxic potential of CD8+ T cells.