Effects of asbestos fibers on human cytotoxic T cells

Abstract

The immunological effects of asbestos have been demonstrated and include reduction of antitumor immunity such as the reduction of natural killer (NK) cell activity with decreased expression of NK cell-activating receptor, NKp46, as well as reduced expression of CXCR3, chemokine receptor, and interferon (IFN)-γ in CD4+ T cells. In this review, the effects of asbestos as demonstrated by our investigations on the cellular characteristics and functions of cytotoxic T lymphocytes (CTLs) differentiated from CD8+ T cells are shown and discussed. Experiments involving in vitro exposure of chrysotile asbestos onto a mixed lymphocyte reaction (MLR) assay to estimate clonal expansion (proliferation and differentiation) of CD8+ T cells revealed the inhibition of both proliferation and differentiation. These results should be interpreted as the impairment of CTL differentiation in the lymph nodes, where asbestos fibers are located continuously in asbestos-exposed people. In addition, analyses of cellular functions in asbestos-exposed patients with pleural plaque (PP) and malignant mesothelioma (MM) are discussed. PP patients showed an increase in effector memory CD8+ T cells compared to healthy donors or MM patients. Furthermore, MM patients showed a decrease in perforin-expressing CD8+ T cells. These results indicated that although asbestos-exposed individuals are ready to respond with transformed cells, CTLs may lose their function once mesothelioma progresses.