Inflammatory Alteration of Human T Cells Exposed Continuously to Asbestos

Abstract

Asbestos is a known carcinogen and exposure can lead to lung cancer and malignant mesothelioma. To examine the effects of asbestos fibers on human immune cells, the human T cell leukemia/lymphoma virus (HTLV)-1 immortalized human T cell line MT-2 was employed. Following continuous exposure to asbestos fibers for more than eight months, MT-2 sublines showed acquisition of resistance to asbestos-induced apoptosis with decreased death signals and increased surviving signals. These sublines showed various characteristics that suggested a reduction in anti-tumor immunity. On the other hand, inflammatory changes such as expression of MMP7, CXCR5, CXCL13 and CD44 was found to be markedly higher in sublines continuously exposed to asbestos compared with original MT-2 cells. All of these molecules contribute to lung inflammation, T and B cell interactions and connections between mesothelial cells and T cells. Thus, further investigation focusing on these molecules may shed light on the role of chronic inflammation caused by asbestos exposure and the occurrence of malignant mesothelioma. Finally, regarding peripheral T cells from healthy donors (HD) and asbestos-exposed patients with pleural plaque (PP) or malignant pleural mesothelioma (MPM), following stimulation of CD4+ T cells, T cells from MPM patients showed reduced potential of interferon (IFN)-γ expression. Moreover, levels of interleukin (IL)-6, one of the most important cytokines in chronic inflammation, in cultured supernatants were higher in PP and MPM patients compared with HD. Overall, asbestos-induced chronic inflammation in the lung as well as the pleural cavity may facilitate the onset of asbestos-induced cancers due to alterations in the interactions among fibers, immune cells such as T and B cells and macrophages, and mesothelial and lung epithelial cells. Further investigations regarding chronic inflammation caused by asbestos fibers may assist in identifying molecular targets for preventive and therapeutic strategies related to the effects of asbestos exposure.

Immune Alteration Caused by Fibrous and Particulate Environmental Substances

“…In another aspect, the effects of asbestos fibers on various human immune cells such as CTL, NK cells, Tresp, and Treg indicated that asbestos exposure reduced the antitumor immunity [55]. This may involve in tumor occurrences and rapid progression of asbestos-induced cancers such as malignant mesothelioma.…”

“…In addition, it was found that matrix metalloproteinase (MMP)-7 gene expression was enhanced in asbestos-exposed subline rather than original line [55]. Although the role of this finding is not explored well, MMP-7 also known as matrilysin is considered as the enzyme related to the cancer metastasis and invasion to cut extracellular matrix such as proteoglycan, fibronectin, and collagen type IV [56].…”

Alteration of Various Lymphocytes by Particulate and Fibrous Substances

“…All findings described in this chapter are summarized in Figure 1. In this review, the effects of silica [67][68][69] and asbestos [64][65][66] are introduced and discussed. However, people are exposed to many more potentially hazardous occupational and environmental substances, such as various materials in air pollutants and a variety of metals in work environments.…”

“…Taken together, continuous and low-dose exposure to asbestos caused a reduction in antitumor immunity in CTLs, NK cells, CD4+ T cells, and Tregs [64][65][66]. Thus, it could be considered that people subjected to continuous, low-dose exposure to asbestos are susceptible to the onset of cancers because of a gradual reduction in antitumor immunity.…”

“…Thus, it could be considered that people subjected to continuous, low-dose exposure to asbestos are susceptible to the onset of cancers because of a gradual reduction in antitumor immunity. Thereafter, certain localized areas such as lung fields or the pleural cavity may become the locus where fibers remain in the body and chronic stimulations may occur at these locations on the basis of reduced antitumor immunity [64][65][66]. This may represent the mechanism by which asbestosinduced cancers occur in the long term, after a latency period of approximately 30-40 years, following initial exposure to asbestos fibers.…”